RTI-909; Project 0209189.000 Final Report 

i

Table of Contents 

Page

QUALITY ASSURANCE STATEMENT ........................................................................... iii 

COMPLIANCE STATEMENT .......................................................................................... v 

ABSTRACT...................................................................................................................... 1 

INTRODUCTION ............................................................................................................. 4 

MATERIALS AND METHODS ......................................................................................... 5 

 Designation of Responsibilities .................................................................................. 5 

 Test Material............................................................................................................... 5

 Animals and Husbandry ............................................................................................. 6 

 Study Schedule and Design....................................................................................... 9 

 Table A. Study Schedule........................................................................................... 9 

 Table B. Number of Animals Assigned to Study Groups........................................... 10 

 Statistics..................................................................................................................... 13 

 Storage of Records .................................................................................................... 15 

 Personnel ................................................................................................................... 15 

RESULTS ........................................................................................................................ 16 

Test Chamber Analyses ............................................................................................. 16 

Maternal Findings....................................................................................................... 17 

Uterine and Embryofetal Findings .............................................................................. 19 

DISCUSSION................................................................................................................... 21 

CONCLUSIONS............................................................................................................... 26 

REFERENCES ................................................................................................................ 28 

LIST OF PROTOCOL DEVIATIONS ............................................................................... 32 

Appendices

Appendix I: HLS Inhalation Report 

Appendix II: Individual Animal Data Tables 

Appendix III: Protocol and 2 Amendments 
RTI-909; Project 0209189.000 Final Report 

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List of Tables 

Page

Table 1 Analysis of Test Atmospheres........................................................................ 34 

Table 2 Summary and Statistical Analysis of the Maternal Body Weights and Body 

 Weight Changes............................................................................................. 35 

Table 3 Summary of the Maternal Clinical Observations ............................................ 41 

Table 4 Summary and Statistical Analysis of the Maternal Feed Consumption.......... 43 

Table 5 Summary and Statistical Analysis of the Maternal Absolute and Relative 

 Organ Weights ............................................................................................... 49 

Table 6 Summary and Statistical Analysis of Ovarian Corpora Lutea, Uterine 

 Contents, Live Fetal Sex and Live Fetal Body Weight ................................... 51 

Table 7 Summary and Statistical Analysis of Fetal External Malformations and 

 Variations ....................................................................................................... 55 

Table 8 Summary of Morphological Abnormalities in CD-1 Mouse Fetuses: 

 Listing by Defect Type.................................................................................... 58 

Table 9 External Malformations in Control CD-1® Mouse Litters From Studies 

 Performed for Governmental Clients at RTI From 1997 to 2002.................... 59 

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RTI-909; Project 0209189.000 Final Report 

GLP COMPLIANCE STATEMENT 

This study was conducted in accordance with the U.S. EPA Good Laboratory Practice 

(GLP) standards for the 21 l(b) program (40 CFR 79; U.S. EPA, 1994), and performed according 

to the protocol (and two amendments) and following the SOPs of HLS and RTI. This study 

complied with all appropriate parts of the USD A Animal Welfare Act regulations: 9 CFR Parts 1 

and 2 Final Rules, Federal Register, Vol. 54, No. 168, August 31,1989, pp. 36112-36163, 

effective October 30, 1989, and 9 CFR Part 3 Animal Welfare Standards; Final Rule, Federal 

Register, Volume 55, No. 32, February 15,1991, pp. 6426-6505, effective March 18,1991. 

It was the Sponsor's responsibility to maintain the method of synthesis, fabrication, or 

derivation of the test fuel, and this was not completed at the time of the study conduct but has 

been completed since and is on file with the Sponsor. 

Rbchelle W. Tyl, Ph.D., DABT Date 

Study Director 

/^ M. Gray, IVLS^DABT ^f ' Date 

^/Sponsor's Representative 
RTI-909; Project 0209189.000 Final Report 

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ABSTRACT 

 This study was conducted to provide a robust evaluation of the developmental toxicity 

potential of an inhaled vapor condensate of gasoline/methyl tertiary butyl ether (G/MTBE) in 

mice. It was conducted in accordance with the U.S. EPA Good Laboratory Practice (GLP) 

standards for the 211(b) program (40 CFR 79; U.S. EPA, 1994). In the mouse study at 

ExxonMobil Biomedical Sciences, Inc. (EMBSI, 2009b), several uncommon ventral closure 

defects (malformations) were observed in a nonexposure responsive incidence. The study 

reported herein was conducted to confirm and/or extend the findings observed in that earlier 

mouse study. 

 Twenty-three plug-positive female CD-1 mice each were distributed on gestational day 

(gd) 0 into the 0, 2000, 10,000, and 20,000 mg/m3

 target concentration groups, and an additional 

38 plug-positive CD-1 mice were distributed on gd 0 into the 30,000 mg/m3 target concentration 

group. Exposures were for 6 hours/day on gd 5 through 16 for the 0-20,000 mg/m3 groups and 

for 6 hours/day on gd 5 through 10 for the 30,000 mg/m3

 group. The females were weighed on 

gd 0 and daily on gd 5 through 17; feed consumption and clinical observations were also 

recorded daily. Clinical observations were recorded individually before and after each exposure 

period and recorded at least once, using general categories (e.g., few, some, most, all, etc.) 

during each exposure period. At scheduled necropsy on gd 17, all dams were euthanized, with 

body weight, gravid uterine weight, liver weight, paired adrenal gland weights, and paired 

kidney weights recorded. Ovarian corpora lutea were counted and uterine total implantations, 

resorptions, late fetal deaths, and live fetuses recorded for each pregnant dam. Each live fetus 

was euthanized by intraperitoneal injection of sodium pentobarbital, sexed, and examined 

externally for gross malformations and variations (including examination for cleft palate). Each 

fetus was then dissected by a ventral longitudinal cut; the thoracic and abdominal viscera were 

removed and retained in buffered neutral 10% formalin for possible subsequent visceral 

examination. The carcasses were skinned after blanching and retained in 70% ethanol for 

possible subsequent staining and skeletal examination. 

 Mean analytical exposure concentrations were 0, 2074, 9925, 20,342 and 29,250 mg/m3

. 

No females died or were sacrificed moribund; 1 female was removed due to a pre-existing 

condition. There were no differences across groups in maternal body weights or weight changes 

before, during, or after the exposure period, except for significant decreases in body weight 
RTI-909; Project 0209189.000 Final Report 

2

change from gd 12 to 13 at 2000 and 20,000 mg/m3

. These findings on gd 12-13 were 

considered incidental and unrelated to treatment since they were observed on only 1 day and not 

in a dose-response pattern. Clinical observations that appeared treatment related included 

labored breathing in 1 female each at 20,000 and 30,000 mg/m3

 and lacrimation in 1 female at 

20,000 mg/m3 and in 3 females at 30,000 mg/m3. Absolute maternal feed consumption (g/day) 

was uniformly decreased at 20,000 and 30,000 mg/m3

 and increased at 10,000 mg/m3 (and at 

30,000 mg/m3 for gd 13-14) in the exposure period, with sporadic increases and decreases in the 

postexposure period in all exposed groups. Relative maternal feed consumption (g/kg body 

weight/day) was reduced at 20,000 and 30,000 mg/m3 during the exposure period (with 

significant increases during exposure at 10,000 mg/m3 [gd 5-6 and 6-7] and at 30,000 mg/m3 [gd 

13-14]), variable during the postexposure period, and unaffected across all groups for the 

gestational period: gd 0-17. These decreased feed consumption effects at 20,000 and 30,000 

mg/m3

 were considered related to exposure to the test material at these exposure concentrations, 

exacerbating effects from the procedures for inhalation exposures, per se (e.g., moving animals, 

removal of feed during exposures). 

 There were no differences in maternal gravid uterine weight or in absolute or relative 

paired adrenal gland weights across groups. Absolute maternal liver weight was significantly 

increased at 10,000 mg/m3, and relative maternal liver weight was significantly increased at 

2000, 10,000, and 20,000 mg/m3, likely due to induction of metabolizing enzymes during gd 5-

16 exposures (Conney, 1967). There were no differences across groups for the number of 

ovarian corpora lutea, uterine implantation sites, resorptions, late fetal deaths or live fetuses per 

litter, or percent preimplantation loss. There were also no statistically significant differences in 

the number (or %) of nonlive (resorptions plus late fetal deaths) or adversely affected (nonlive 

plus malformed) implantations/litter, although there were 3 (of 36) females with fully resorbed 

litters at 30,000 mg/m3

 (with 0, 1, 0, and 2 fully resorbed litters at 0, 2000, 10,000, and 20,000 

mg/m3

, respectively). 

 For live litters, there were no differences across groups on the number of live 

fetuses/litter, % male fetuses/litter, number of male and female fetuses/litter, or on average fetal 

body weight per litter for all fetuses or by sexes separately. There were no statistically 

significant differences across groups for incidences of external malformation or variations by 

fetuses or by litter. External fetal malformations included encephalocoele in 1 fetus (in 1 litter) 
RTI-909; Project 0209189.000 Final Report 

3

at 2000 mg/m3

 and cleft palate in 2 fetuses (in 2 litters) at 0 mg/m3, in 1 fetus (in 1 litter) each at 

2000, 10,000, and 20,000 mg/m3, and in 7 fetuses (in 4 litters) at 30,000 mg/m3. The increased 

incidence of cleft palate at 30,000 mg/m3

 was not statistically significant; it is likely due to 

increased maternal stress and other toxicity at this exposure concentration during the 6-day 

exposure period, during the time of initial palatal formation (gd 5-10). Gastroschisis was also 

observed in 1 female fetus (in 1 litter) at 30,000 mg/m3

 (this female also had cleft palate). Fetal 

external variations included abnormal rugae in the palatal midline in 1 fetus (in 1 litter) each at 

10,000 and 20,000 mg/m3

, and hematomas of the face, head, neck, and shoulder at 0-20,000 

mg/m3

 (but not at 30,000 mg/m3). The external variations are considered incidental and 

unrelated to treatment. 

 In conclusion, the current study did not confirm the presence of ectopia cordis observed 

in a previous EMBSI (2009b) study in any fetus in any litter of any group, and therefore this fetal 

finding is considered unlikely to be related to maternal exposure to the test material. In addition, 

the study did not confirm the presence of gastroschisis in fetuses at 10,000 mg/m3 (observed in 

the EMBSI study) or at 2000 or 20,000 mg/m3

 (not observed in the EMBSI study or in the 

present study). Gastroschisis was observed in 1 female fetus in 1 litter at 30,000 mg/m3; she also 

exhibited severely reduced body weight and cleft palate and was part of a litter with 2 other 

fetuses with cleft palate. In total, gastroschisis was observed in 1 fetus (out of 407 fetuses; 

0.24%) in 1 litter (out of 33 litters; 3.03%) at 30,000 mg/m3, and there was an increased 

incidence (not statistically significant) of cleft palate (7 fetuses in 4 litters), likely from maternal 

stress also at 30,000 mg/m3

. Cleft palate is the most common external malformation observed in 

mouse fetuses. Maternal treatment-related clinical signs of distress, consisting of labored 

breathing observed at 20,000 and 30,000 mg/m3

, likely produced an increased incidence of cleft 

palate at 30,000 mg/m3

. This increase in cleft palate is interpreted as likely to be secondary to 

maternal stress (during the gd 5-10 exposure period), which would likely result in increased 

corticosteroid synthesis (and cleft palate, as noted in the published literature; e.g., Carmichael et 

al., 2007; Senda et al., 2005; Pradat et al., 2003; Hemm et al., 1977). The increased 

corticosteroid levels likely would have resolved in this group by scheduled necropsy on gd 17. 

The results of this study indicate that the effects on fetuses at 30,000 mg/m3

 were most likely due 

to or exacerbated by maternal toxicity. The absence of gastroschisis in any of the 3,641 control 

CD-1 mouse fetuses, in 288 control litters, in RTI’s historical control database (Table 9) lends 
RTI-909; Project 0209189.000 Final Report 

4

support to the conclusion that gastroschisis may have been treatment related, occurring in only 1 

compromised fetus at 30,000 mg/m3

, with concomitant other fetotoxicity and some indication of 

maternal toxicity. Indication of slight fetotoxicity (gastroschisis in 1 compromised fetus) only at 

30,000 mg/m3 and of maternal toxicity (labored breathing) at 20,000 and 30,000 mg/m3 in this 

study results in the following determinations: the maternal toxicity No Observable Adverse 

Effect Level (NOAEL) was 10,000 mg/m3

, and the developmental toxicity NOAEL was 20,000 

mg/m3. 

INTRODUCTION 

 A very early inhalation toxicity study of MTBE for 6 hours/day on gd 6-15 in SpragueDawley rats and CD-1 mice showed no maternal or embryofetal effects at any exposure 

concentration in rats (Conaway et al., 1985). In mice, there were increases in fetal resorptions at 

the low (250 ppm) and high (2500 ppm) concentrations, attributed to 2 females in each group 

with a high number of resorptions. There were no treatment-related fetal external, visceral, or 

skeletal malformations or variations. Slightly increased sternebral fusions in the high 

concentration group were “attributed to fetotoxicity”. 

 A previous developmental toxicity study (EMBSI, 2009b) of G/MTBE vapor condensate 

by inhalation in mice was one of a series of tests required in accordance with the Alternative Tier 

2 provisions of fuels and fuels additives health effects testing regulations (U.S. EPA, 1994, 40 

C.F.R. § 79; Oge 1998). That study provided suggestive evidence of an increase (not statistically 

significant or exposure related) in midline defects among the offspring of dams exposed to 

G/MTBE by inhalation at the low and mid (but not high) vapor concentrations, reporting 

gastroschisis and ectopia cordis (2 very rare external malformations) in offspring at these 

exposure concentrations in the absence of dose-response patterns. That study involved wholebody inhalation exposure of timed-pregnant CD-1 mice for at least 6 hours/day, on gd 5 through 

17, to baseline gasoline vapor condensate with 25.5% MTBE at target concentrations of 0, 2000, 

10,000, and 20,000 mg/m3 (the last is 50% of the lower explosive limit). 

 The purpose of the present study was to provide maternal and developmental toxicity data 

relative to a 6- or 12-day exposure regimen of inhaled G/MTBE during the period of early or 

major organogenesis in gravid mice in order to confirm and extend the findings observed in the 

EMBSI mouse study (2009b). The present study was conducted with the same exposure 
RTI-909; Project 0209189.000 Final Report 

5

concentrations used in the EMBSI study (2009b) for 6 hours/day on gd 5 through 16 (23 

females/group) and an additional group of 38 timed-mated mice exposed to 30,000 mg/m3

 for 6 

hours/day on gd 5 through 10. Fetal malformations of specific interest in this study (ventral wall 

closure defects) are formed early in the embryonic period of gestation; gd 7 through 9 in the 

mouse (e.g., Rugh, 1968), hence the shortened exposure period for this group. A range-finding 

study was previously conducted to evaluate the top exposure level and exposure duration to be 

used in this study (RTI, 2009). 

MATERIALS AND METHODS 

Designation of Responsibilities

RTI International was responsible for study design, protocol generation, designed the 

procedures and trained the Huntingdon Life Sciences (HLS) staff for pairing and detection of 

successful mating, assignment of plug-positive study females to groups, necropsy of the maternal 

and fetal animals on gd 17, generation of summary and individual data tables, and draft and final 

reports (with RTI QA oversight). RTI’s Quality Assurance Unit performed a prestudy on-site 

inspection, reviewed the protocol and any amendments, and monitored all phases of the study in 

which RTI personnel participated. HLS was responsible for receipt of the test material, prestudy 

and study generation and analyses of the test vapors, receipt, quarantine and housing of the test 

females and breeder males, determining the successful mating and assignment of the study 

females, in-life observations, loading and unloading study females into and out of chambers, and 

submission of interim and final inhalation reports. The Quality Assurance Unit of HLS reviewed 

the protocol and monitored the facilities, equipment, personnel, methods, practices, records, raw 

data, draft and final inhalation reports, and controls used in this study to assure that they were in 

conformance with company standard operating procedures and the referenced GLP regulations. 

Test Material

 The test material, G/MTBE (MRD-00-713; “API 211BG with MTBE Vapor 

Condensate”), was a colorless liquid and identified by the supplier (Chevron Global Technology 

Services Company (CRTC; Richmond, CA) as Lot/Batch Number API 00-02. Methods of 

synthesis, fabrication, or derivation were documented by the Sponsor and located at API. 

Information on identity, strength, purity, and composition of G/MTBE was provided by the 
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6

Sponsor and documented in the raw data and in this final report (Appendix III, protocol 

attachment). 

Two separate types of chemical analysis were performed on the test material. CRTC 

conducted proprietary characterization of all 120 components. EMBSI conducted a GLP-compliant 

characterization of 18 representative hydrocarbons and MTBE. In the CRTC method, the weight 

percent of each of the components was measured, whereas in the EMBSI method, the relative 

amount of each of the representative components was measured on area-percent basis. 

EMBSI developed their method for API to share with CRTC and the laboratories performing 

toxicological studies on 211(b) testing program test substances. The objective of the method was to 

monitor and document the chemical and compositional stability of G/MTBE from manufacture 

through transportation, storage, and animal exposure using a standard method that all users could 

perform. 

The test material was stable and stored under ambient conditions in an outside solvent shed 

except when in use in the inhalation laboratory. The test substance was handled as a flammable 

liquid. Detailed information on chemical handling is provided in the MSDS attached to the 

protocol (Appendix III). 

Animals and Husbandry

 The test animals were Caesarean-originated Virus Antibody Free (VAF) Crl:CD-1®

(ICR) BR outbred albino mice supplied by Charles River Laboratories, Inc., Raleigh, NC. The 

use of live animals was requested by the Sponsor and required by U.S. EPA OPPTS Testing 

Guidelines (U.S. EPA, 1998). Alternative test systems are not available for the assessment of 

chemical effects on prenatal mammalian development. The Charles River CD-1® mouse has 

been the mouse strain of choice on developmental toxicology contracts at RTI since 1976. Large 

historical databases for reproductive performance and prevalence of spontaneous malformations 

in control mice are available from studies conducted at RTI (currently based on 288 control 

litters and over 3600 fetuses from 16 studies). 

 One hundred seventy (170) nulliparous female mice were ordered for this study and 

arrived at HLS on December 23, 2004. One hundred (100) male mice, 9-11 weeks old upon 

arrival at HLS (on August 31, 2004), of the same strain and from the same supplier, were 

received for the previous range-finding study, and the remaining 99 males were used as a male 

breeding colony for this study. The exact number of females ordered was received, so there were 
RTI-909; Project 0209189.000 Final Report 

7

no replacements available. However, there were no animals with clinical signs, injury, and/or 

reduced feed consumption during quarantine. The 99 males were used to generate timed-mated 

animals for this definitive developmental toxicity study, which required the mating of 170 female 

mice (1:1, with the subsequent addition of naïve females to males who inseminated their original 

females) to generate 130 plug-positive females. Females were 7-9 weeks old at arrival and 9-11 

weeks of age and ~20-35 g in weight on gd 0. One hundred seventy (170) females were required 

to generate 130 plug-positive females in 11 consecutive days (the protocol indicated that we 

expected 130 plug-positive females in 4-5 days, but it took longer; Amendment 2); 130 plugpositive females (23/group for 4 groups and 38/group for the fifth group) were required to supply 

the optimal number (based on EPA’s guidance; e.g., OPPTS 870.3600; U.S. EPA, 1996; for 

inhalation developmental toxicity studies) of pregnant animals and litters to assess any maternal 

and/or embryo/fetal toxicity to the test substance and to confirm and extend the fetal findings 

from the previous EMBSI study (2009b). 

 During an approximately 14-day quarantine/acclimation period at the HLS testing facility, 

animals were checked for viability twice daily. Prior to study assignment, all animals were 

examined to ascertain suitability for study. The HLS veterinarian formally released these 

animals for use by signature and date. Males and females were individually housed in stainless 

steel suspended cages with wire mesh floors and fronts, except for the mating period when 

1 male and 1 female were housed together. During cohabitation, male and female mice were 

housed in polycarbonate “shoebox” cages with stainless steel lids and Alpha-Dri® bedding 

(Shepherd Specialty Papers, Watertown, TN). Each cage was fitted to secure a glass feeder jar 

with a stainless steel lid. Clean feed jars and fresh feed were provided at least weekly. After the 

gd 14 exposure (for Groups 1-4) or on the afternoon of gd 14 (Group 5), a stainless steel, 

perforated insert was placed on the wire-mesh floor of the stainless steel suspended cage of each 

female and 1 Nestlet® (Ancare, Bellmore, NY) added to each cage until scheduled sacrifice on 

gd 17. Females not undergoing daily exposures after gd 10 (Group 5) were removed from their 

home cage and placed in another suspended cage without feed to match as closely as possible the 

conditions of Group 1-4 females for the 6-hour exposure period. They were then returned to 

their home cage at the same time as the exposed females for feed measurement overnight. Feed 

(PMI 5002 Certified Meal) was available ad libitum, except during the daily 6-hour inhalation 

periods. Analytical certifications of batches of feed provided by the manufacturer are maintained 
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8

on file at the HLS testing facility, and there were no known contaminants found in the feed. 

Facility water (supplied by Elizabethtown Water Company, Westfield, NJ) was available ad 

libitum via the automatic watering system or water bottles (during mating), except during the 

daily 6-hour inhalation periods. Water analyses were conducted by Elizabethtown Water 

Company to assure that water met standards specified under the EPA Federal Safe Drinking 

Water Act Regulations (40 CFR Part 141). Water analyses provided by the supplier are 

maintained on file at the HLS testing facility. There were no known contaminants that interfered 

with the objectives of this study. At all times, animals were housed, handled, and used according 

to the National Research Council Guide (NRC, 1996). 

A 12-hour light/dark cycle was provided via automatic timer. Temperature and relative 

humidity were monitored in accordance with Testing Facility SOPs to ensure that the desired 

range of 18 to 26°C for temperature and 30 to 70% relative humidity was maintained to the 

maximum extent possible (NRC, 1996). 

 Each animal was assigned a temporary identification number (designated on each cage) 

upon receipt. During the second week of the quarantine/acclimation period, the 170 females 

received were tail tattooed with consecutive numbers 1 through 170. The 99 remaining males 

had been tail tattooed during the range-finding study with consecutive numbers 1 through 100 

(except for No. 87). After selection for use on the study, mating, indication of copulation, and 

assignment to 1 of the five groups, each female was ear tagged with a number assigned by the 

HLS testing facility. This number, plus the study number, comprised the unique animal number 

for each animal. Each cage was provided with a cage card that was color coded for exposure 

level identification and contained the study and animal numbers. 

 It was anticipated that the concentrations employed would not result in irritation or 

corrosion to the respiratory tract of the test animals (based on previous studies with the test 

material; e.g., Conaway et al., 1985; Bevan et al., 1997a; EMBSI, 2008, 2009a,b). Animals were 

not subjected to undue pain or distress. All procedures used in this study were designed to avoid 

discomfort, distress, and pain to the animals. The HLS IACUC (Institutional Animal Care and 

Use Committee) Protocol Review Subcommittee and the RTI IACUC reviewed the protocol and 

found it to be in compliance with appropriate animal welfare regulations. 

 Immediately prior to pairing, each female was weighed and subjected to a clinical 

examination. For breeding, 1 male with 1 female pairing was employed since other pairing 
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patterns (e.g., 1 male with 2 females) may have resulted in an unacceptable number of plugpositive, nonpregnant females and/or sire effects. Individual females were placed in 

polycarbonate “shoebox” cages with stainless steel lids with singly-housed males. On the 

following morning and each morning thereafter, the females were examined for the presence of a 

vaginal copulation plug (Hafez, 1970). The day on which copulation plugs were found was 

designated as gd 0. Plug-positive females (dams) were individually housed until scheduled 

sacrifice on gd 17. Plug-negative females were retained in the same male's cage and checked for 

plugs on successive mornings until insemination occurred or the treatment groups were filled, 

whichever came first. HLS staff evaluated females for vaginal copulation plugs until all groups 

were filled and then completed the exposure schedule. When all treatment groups were filled, 

the remaining presumed plug-negative females were sacrificed by asphyxiation with CO2 and 

examined for pregnancy status; many of the females were in fact pregnant (see Protocol 

Deviation No. 7). The males were also euthanized by HLS staff after the breeding period was 

completed. The fate of all animals is fully documented in the study records. 

Study Schedule and Design

 The actual dates of all major phases of the study are presented in Table A. 

Table A. Study Schedule 

Event Dates 

 Females arrived at HLS: December 23, 2004 

 Quarantine (14 days): December 23, 2004 – January 5, 2005 

 Animals paired: January 6-11, 2005 

 Dates of gd 0: January 7-17, 2005 

 TSCA experimental start date: January 12, 2005 

 Exposure dates: gd 5 through 10 January 12 – January 22, 2005 

 gd 5 through 16 January 12 – February 2, 2005 

 Terminal necropsy (gd 17) January 24 – February 3, 2005 

 TSCA experimental termination date: February 3, 2005 

 Submission of draft data on test 

 atmospheres to Sponsor: February 9, 2005 (within 1 week after the last 

exposure date, February 2, 2005) 
RTI-909; Project 0209189.000 Final Report 

10

 This study was conducted with 4 treatment groups and 1 vehicle control group. Groups 

1-4 were each comprised of 23 plug-positive female mice, and Group 5 was comprised of 38 

plug-positive female mice (Table B). 

Table B. Number of Animals Assigned to Study Groups 

Group No. No. Animals 

Exposed 

No. Days 

Exposed 

Exposure Period 

(gd) 

Target Exposure 

Concentration (mg/m3

) 

1 23 12 5 through 16 0 

2 23 12 5 through 16 2000 

3 23 12 5 through 16 10,000 

4 23 12 5 through 16 20,000 

5 38 6 5 through 10 30,000 

The exposure period for Group 5, at 30,000 mg/m3 G/MTBE on gd 5 through 10, was 

selected to reduce the number of days of generation of test atmosphere at a concentration that 

was 75% of the lower explosive limit. In addition, the fetal malformations of interest are formed 

early in the embryonic period of gestation; gd 7-9 in the mouse (e.g., Rugh, 1968), so extending 

the exposure period to gd 16 was considered unnecessary. 

 The test substance was administered as a vapor in the breathing air of the animals. The test 

atmosphere was generated by an appropriate procedure determined during prestudy trials. The 

prestudy trials were performed (at least two 6-hour periods) to evaluate the optimal set of 

conditions and equipment to generate a stable atmosphere at the target exposure levels and 

maintain uniform conditions throughout the exposure chambers. The whole-body exposure 

chambers each had a volume of approximately 1000 liters. The chambers were operated at a 

minimum flow rate of 200 liters per minute. The final airflow was set to provide at least 1 air 

change in 5 minutes (12 air changes/hour) and a T99 equilibrium time of at most 23 minutes. This 

chamber size and airflow rate was considered adequate to maintain the oxygen level at least 19% 

and the animal loading factor below 5%. At the end of each daily 6-hour exposure, all animals 

remained in the chamber for a minimum of the T99 equilibrium time. During this time, the chamber 

was operated at approximately the same flow rate using clean air only. 

 A nominal exposure concentration of G/MTBE was calculated. The flow of air through the 

chamber was monitored using appropriate calibrated equipment. The test substance consumed 
RTI-909; Project 0209189.000 Final Report 

11

during the exposure was divided by the total volume of air passing through the chamber (volumetric 

flow rate times total exposure time) to give the nominal concentration. 

 During each 6-hour exposure, measurements of airborne concentrations were performed in 

the animals’ breathing zone at least 4 times using an appropriate sampling procedure and IR 

analytical procedure. Specified airborne test material concentrations were within +/- 10% of the 

target concentrations. One sample per chamber during the trials period and the treatment period 

was analyzed by gas chromatography to characterize at least 10 major components (comprising at 

least 80% by weight of the test substance) to show test substance stability and comparison between 

the neat liquid test substance and the vaporized test atmospheres. During the treatment period, 

particle size determinations were performed once per chamber using a TSI Aerodynamic Particle 

Sizer to confirm the absence of particulate test substance condensate in the exposure atmosphere. 

 Chamber temperature, humidity, airflow rate, and static pressure were monitored 

continuously and recorded every 30 minutes during exposure. Chamber temperature and relative 

humidity were maintained, to the maximum extent possible, between 20 to 24°C and 40 to 60%, 

respectively. Chamber oxygen levels (maintained at least 19%) were measured pretest and at the 

beginning, middle, and end of the exposure period for the study. Air samples were taken in the 

vapor generation area pretest and at the beginning, middle, and end of the exposure period for the 

study. Light (maintained approximately 30 foot-candles at 1.0 meter above the floor) and noise 

levels (maintained below 85 decibels) in the exposure room were measured pretest and at the 

beginning, middle, and end of the exposure period for the study. The minimum frequency of 

chamber activity during the treatment period is summarized below: 

Activity Frequency/Chamber 

Measured test substance concentration 4X/day 

Measured test substance characterization 1X 

Particle size 1X 

Temperature 13X/day 

Relative humidity 13X/day 

Airflow rate 13X/day 

Static pressure 13X/day 

Nominal test substance concentration (excluding the air control chamber) 1X/day 

Rotation pattern of exposure cages 1X/day 

Loading/unloading verification 1X/day 
RTI-909; Project 0209189.000 Final Report 

12

 Plug-positive female mice (dams) were assigned to treatment groups by a stratified 

randomization method designed to provide uniform mean body weights and equal distribution of 

females mated to the same male among dose groups using data from gd 0. A total of 23 plugpositive dams were assigned on gd 0 by stratified randomization (by body weight) to each of 4 

groups (0 [Group 1], 2000 [Group 2], 10,000 [Group 3], and 20,000 [Group 4] mg/m3), and 38 

plug-positive dams were similarly assigned to Group 5 (30,000 mg/m3

). Because of the 

unexpectedly prolonged mating period, the decision was made at HLS (see Protocol Deviation 

No. 2) to use 130 plug-positive females rather than wait for 140 plug-positive females, and use 

23/group (versus 25/group) for Group 4 and 38/group (versus 40/group) for Group 5. Plugpositive females were exposed to G/MTBE or air 6 hours per day from gd 5 through 16 for 

Groups 1-4 and for gd 5 through 10 for Group 5, 30,000 mg/m3

, since the malformations of 

interest (gastroschesis and ectopia cordis) result from ventral midline closure defects early in the 

embryologic period, and the shorter exposure period could possibly reduce the risk of prenatal 

deaths, which could limit the ability of the study to detect these early malformations. For each 

daily exposure, females were transferred to inhalation cages, and the cages were moved into the 

appropriate chambers for exposure. Following each daily exposure, females were transferred 

back to home caging for feed consumption measurements overnight. 

 Clinical observations of all animals were made once daily on gd 0 through 4 (prior to the 

start of the exposure period), twice daily (prior to and immediately after each daily exposure) 

throughout the exposure period (gd 5 through 10 or gd 5 through 16), and once daily on gd 11 

through 17 or on gd 17 (after exposure period ended). In addition, during each daily exposure 

period, animals were observed at least once during each exposure. This was routinely performed 

near the middle of each exposure. 

 Dams were weighed in the mornings (prior to exposures for those days that exposures 

occurred) on gd 0 and 5-17. Maternal weight gains were calculated for gd 0-5 (pre-exposure 

period), gd 5-6, 6-7, 7-8, 8-9, 9-10, 10-11, 11-12, 12-13, 13-14, 14-15,15-16, gd 5-10 or 5-16 

(exposure period), gd 10-17 or 16-17 (postexposure period), and gd 0-17 (gestational period). 

 Maternal feed consumption was evaluated in the mornings from gd 0-5 (pre-exposure 

period), gd 5-6, 6-7, 7-8, 8-9, 9-10, 10-11, 11-12, 12-13, 13-14, 14-15, 15-16, gd 5-10 or 5-16 

(exposure period), 10-17 or 16-17 (postexposure period), and gd 0-17 (gestation period). 
RTI-909; Project 0209189.000 Final Report 

13

 On gd 17, approximately 1 to 11⁄2 days before expected parturition, all surviving maternal 

animals from all groups were killed by CO2 asphyxiation at HLS by RTI staff. The thoracic and 

abdominal cavities and organs were examined, and pregnancy status was confirmed by uterine 

examination. Uteri that presented no visible implantation sites were stained with ammonium 

sulfide (10%) in order to visualize any implantation sites that may have undergone very early 

resorption (Salewski, 1964). At sacrifice, the body, liver, uterus, paired adrenal glands, and 

paired kidneys of each plug-positive female were weighed. Ovarian corpora lutea were counted 

and uterine contents (i.e., number of implantation sites, early and late resorptions, dead fetuses, 

live fetuses) recorded. 

 Live and dead fetuses were removed from the uterus, counted, weighed, sexed externally, 

and examined externally for gross malformations (including cleft palate) and variations by RTI 

staff. Each fetus was killed by intraperitoneal injection of sodium pentobarbital. Live and dead 

fetuses were dissected longitudinally, and the thoracic and abdominal viscera removed intact and 

retained individually in labeled scintillation vials in buffered neutral 10% formalin for possible 

subsequent visceral examination. The fetal carcasses were blanched, skinned, and retained in 

individually labeled scintillation vials in 70% ethanol for possible subsequent double staining 

(alizarin Red S and alcian blue) and skeletal evaluation. All maternal organs and carcasses were 

destroyed by incineration. 

Statistics

The unit of comparison was the pregnant female or litter. Quantitative continuous data 

(e.g., maternal body weights, feed consumption, fetal body weights, etc.) were compared among 

the 4 treatment groups and 1 vehicle control group using either parametric ANOVA under the 

standard assumptions or robust regression methods (Zeger and Liang, 1986; Royall, 1986; 

Huber, 1967), which do not assume homogeneity of variance or normality. If the ANOVA test 

was statistically significant (i.e., if one or more of the pairwise comparisons, not necessarily to 

the vehicle control group, were statistically significant), then statistical pairwise comparisons 

were made (see below). The homogeneity of variance assumption was examined via Levene’s 

Test (Levene, 1960), which is more robust to the underlying distribution of the data than the 

traditional Bartlett’s Test. If Levene’s Test indicated lack of homogeneity of variance (p<0.05), 

robust regression methods were used to test all treatment effects. The heterogeneous variance 
RTI-909; Project 0209189.000 Final Report 

14

models (also known as robust regression methods) use variance estimators that make no 

assumptions regarding homogeneity of variance or normality of the data. They were used to test 

for overall treatment group differences (via Wald Chi-Square Tests), followed by individual ttests for exposed vs. control group comparisons when the overall treatment effect was 

significant. At the time these methods were implemented in this study, the software did not have 

p-value adjustments for multiple pairwise comparisons. This problem was recognized, and to 

protect against spurious findings, the significance of individual pairwise comparisons to controls 

(repeated t-tests) were not reported for a given parameter unless the overall treatment effect was 

statistically significant at p<0.05 (Wald chi-square Test). The presence of linear trends was 

analyzed by robust regression methods for nonhomogenous data. Robust regression methods are 

available in the REGRESS procedure of SUDAAN® Release 8. (RTI, 2001). 

If Levene’s Test did not reject the hypothesis of homogeneous variances, standard 

ANOVA techniques were applied for comparing the treatment groups. The GLM procedure in 

SAS® Release 8 was used to evaluate the overall effect of treatment and, when a significant 

treatment effect was present, to compare each exposed group to control via Dunnett’s Test 

(Dunnett, 1955, 1964). Prior to GLM analysis, an arcsine-square root transformation was 

performed on all litter-derived percentage data (Snedecor and Cochran, 1967) to allow use of 

parametric methods. For the litter-derived percentage data, the ANOVA was weighted according 

to litter size. The presence of linear trends was analyzed by GLM procedures for homogenous 

data (SAS Institute Inc., 1999a, b, c, d, e; 2000; 2001). A one-tailed test (i.e., Dunnett’s Test) 

was used for all pairwise comparisons to the vehicle control group, except that a two-tailed test 

was used for maternal body and organ weight parameters, maternal feed consumption, fetal body 

weight, and percent males per litter. Standard ANOVA methods, as well as Levene’s Test, are 

available in the GLM procedure of SAS® Release 8 (SAS Institute Inc., 1999a, b, c, d, e; 2000; 

2001). 

Nominal scale measures were analyzed by Chi-Square Test for Independence for 

differences among treatment groups (Snedecor and Cochran, 1967) and by the CochranArmitage Test for Linear Trend on Proportions (Cochran, 1954; Armitage, 1955; Agresti, 1990). 

When Chi-Square revealed significant (p<0.05) differences among groups, then a Fisher’s Exact 

Probability Test, with appropriate adjustments for multiple comparisons, was used for pairwise 

comparisons between each treatment group and the control group. 
RTI-909; Project 0209189.000 Final Report 

15

A test for statistical outliers (SAS Institute, Inc., 1999b) was performed on female body 

weights, feed consumption (in g/day), and selected organ weights. Per RTI’s SOPs, if 

examination of pertinent study data did not provide a plausible, biologically sound reason for 

inclusion of the data flagged as “outlier,” then the data were excluded from summarization and 

analysis and designated as outliers. If there was a plausible, biologically sound reason to retain 

the flagged data, the data were included in the summarization and analysis. Unless otherwise 

specified, the level of significance used for the various tests was p<0.05. 

Storage of Records

 All data documenting experimental details and study procedures and observations were 

recorded and maintained as raw data. At the completion of the study, all reports, raw data, 

preserved specimens, and retained samples will be maintained in RTI’s secure archives for a 

period of 1 year after submission of the signed final report. The Sponsor will be contacted in 

order to determine the final disposition of these materials. 

Personnel

 This study was conducted by RTI under contract to the API (Mr. T.M. Gray, Sponsor’s 

Representative) at HLS (Mr. G.M. Hoffman, Principal Investigator; Animal Research Facility 

Veterinarian, Dr. Teresa S. Kusznir; Animal Research Facility Director, Mr. I. Vanterpool; 

Necropsy Laboratory Supervisor, Ms. G.E. Baxter; Inhalation Laboratory Supervisor, Mr. S. 

Cracknell; Formulation Chemistry Services, Ms. K. Saladdin; Reproductive Consultant, Mr. K.P. 

Hazelden; and Quality Assurance, Ms. N.S. Iacono). Dr. R.W. Tyl of RTI served as Study 

Director. RTI Reproductive and Developmental Toxicology personnel included Ms. M.C. Marr 

(Laboratory Supervisor), Ms. C.B. Myers (Reproductive Toxicity Study Supervisor and Data 

Analyst), Mr. W.P. Ross, Mr. C.G. Leach, Ms. L.L. Macdonald, Ms. N.M. Kuney, and Ms. A.J. 

Parham. RTI Quality Assurance personnel were Ms. D.A. Drissel (Manager), Ms. C.A. Ingalls, 

Ms. M.M. Oh, and Ms. S.C. Wade. Mr. W.P. Ross, Ms. N.M. Kuney, Mr. C.G. Leach, Ms. L.L. 

Macdonald, and Ms. M.C. Marr were present at HLS to perform the necropsy and external fetal 

evaluations. Ms. S.C. Wade was also present to observe the procedures and evaluations. 

 The final report was prepared by Dr. R.W. Tyl and Ms. M.C. Marr, with assistance from 

Ms. C.B. Myers for statistical analyses and generation of tables, and by Mr. T.W. Wiley for data 
RTI-909; Project 0209189.000 Final Report 

16

entry. Ms. M.C. Marr was responsible for all transfer of custody procedures for transfer of 

records and tissues from HLS to RTI, and for archiving the study records at RTI. 

RESULTS 

Test Chamber Analyses

Table 1, Appendix I 

Prestudy chamber distribution analyses showed that the test substance was evenly 

distributed within the chamber. Prestudy and in-study chamber monitoring showed that the 

chamber oxygen levels were 20%. 

The analytically measured exposure levels of the airborne test substance were reasonably 

close to the targeted exposure levels. The measured and nominal concentrations varied 

somewhat (less than 10%), but reasonably, from the expected 1:1 ratio for this type of vapor 

exposure. Chamber environmental conditions averaged 20.8oC temperature and 29.6% (based on 

RTI calculations; 29.2% from HLS calculations) relative humidity. Mean particle size 

distribution measurements for the exposures indicated that the atmospheres were essentially 

vapor only, as expected, since there was no substantial difference between the test substance 

chamber and the air control chamber for particle size distribution. 

Analysis of the major components in the neat test substance and the test atmospheres 

showed a reasonably close concordance between the neat test substance and the vaporized test 

substance. These data demonstrated that the test animals were exposed, as expected, to all of the 

major components of the test substance in their proper proportions. The data were consistent 

between the prestudy and in-study analyses, indicating stability of the test substance and the 

atmosphere generation techniques. 

 The test atmospheres were generated to within 97.5 to 103.7% of the target (grand mean 

of daily means/chamber). There was no test material detected in the control chamber, with an 

estimated limit of quantification (LOQ) of 433 mg/m3 (see HLS Study File Note in Appendix I; 

last page). The relative content of MTBE was 21.3%, as provided by the supplier (see Appendix 

III, attachments to protocol). The analytical profile of G/MTBE at HLS indicated 26-27% 

MTBE, confounded by coelution with 2,3-dimethylbutane, which could not be separated using 

gas chromatography with a flame ionization detector and a previously used Supelco PetrocolTM
RTI-909; Project 0209189.000 Final Report 

17

column for the range-finding study (range-finding final study report, Appendix I, HLS report), 

and ~23-25% MTBE (confounded by coelution with 3-methylpentane) using a new column for 

this endpoint-specific developmental toxicity study (see Appendix I, HLS report). Net MTBE 

concentrations were 21.66-22.72% (Appendix I, Table I). 

Maternal Findings

Tables 2-5, Appendix II 

 One female (No. 3814) at 10,000 mg/m3 was removed from study due to a pre-existing 

condition (right side undescended testis, seminal vesicle and prostate, left side ovary, oviduct, 

uterus, cervix and vagina). No females died or were euthanized moribund. The numbers of 

confirmed nonpregnant females (at scheduled sacrifice) were 0, 1, 3, 1, and 2 and fully resorbed 

litters were 0, 1, 0, 2, and 3 at 0, 2000, 10,000, 20,000, and 30,000 mg/m3

, respectively. The 

number (and %) pregnant were 23 (100.0), 22 (95.7), 19 (86.4), 22 (95.7), and 36 (94.7) at 0, 

2000, 10,000, 20,000, and 30,000 mg/m3

, respectively (Table 2). There were no statistically or 

biologically significant differences between groups for % pregnant. 

There were no effects of exposure across all groups on maternal body weights for gd 0, 5, 

6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 (in-life), and gd 17 (at sacrifice). Maternal body weight 

changes were also unaffected across all groups for the following intervals: gd 0-5 (pre-exposure 

period for all groups), gd 5-10 (exposure period for Group 5), gd 5-16 (exposure period for 

Groups 1-4), gd 10-17 (postexposure period for Group 5), gd 16-17 (postexposure period for 

Groups 1-4), and gd 0-17 (gestation period), except for decreased maternal body weight changes 

for gd 12-13 at 2000 (p<0.01) and 20,000 (p<0.05) mg/m3

 (with exposures on gd 5-16). These 

findings were only for 1 day at the lowest and next to the highest exposure concentrations 

(during the exposure period for Groups 1-4) and are considered incidental since they only 

occurred once and did not display a dose-response pattern. Maternal gestational weight change 

(gestational body weight gain minus gravid uterine weight) was unaffected across all groups 

(Table 2). 

 Maternal clinical observations for gd 0-4 (pre-exposure period), prior to and after each 

daily exposure period (gd 5-16 for Groups 1-4 or gd 5-10 for Group 5) and postexposure (gd 17 

for Groups 1-4 or gd 10-17 for Group 5), are presented in Table 3. There were no clinical 

observations of interest recorded for any dam in any group during the daily exposures. Moderate 
RTI-909; Project 0209189.000 Final Report 

18

alopecia on extremities/snout was observed starting on gd 5 in 1 female (No. 4807) at 20,000 

mg/m3

. Enophthalmos (eyeball sunk into orbital cavity), left, was observed in 1 female (No. 

5829) at 30,000 mg/m3

. Labored breathing was observed on gd 9 postexposure for 1 female (No. 

4823) at 20,000 mg/m3

 and on gd 10 postexposure for 1 female (No. 5838) at 30,000 mg/m3. 

Lacrimation, either unilateral or bilateral, was observed for a total of 1 female (No. 4803) at 

20,000 mg/m3

 and 3 females (Nos. 5802, 5805, and 5824) at 30,000 mg/m3. Unilateral moderate 

lacrimation was observed in 1 female (No. 5824) at 30,000 mg/m3 postexposure on gd 5, and 

2 females (1 each at 20,000 [No. 4803] and at 30,000 [No. 5802] mg/m3

) postexposure on gd 6, 

possibly treatment and dose related. Bilateral moderate lacrimation was observed in 1 female 

(No. 5805) at 30,000 mg/m3

 postexposure on gd 6. Lacrimation and labored breathing, observed 

in more than one female at 20,000 and 30,000 mg/m3

, appeared to likely be treatment related. 

Also, red exudates were observed from the anogenital area of 2 females with resorptions: 1 

female each at 10,000 mg/m3 (No. 3808 with 2 mid resorptions) on gd 12 pre-exposure and at 

20,000 mg/m3 (No. 4814 with 1 mid resorption) on gd 11 postexposure (Table 3). 

Maternal feed consumption (in g/day) was significantly reduced at 20,000 mg/m3

 for 

gd 0-5 (pre-exposure period), significantly increased at 10,000 mg/m3 for gd 5-6, significantly 

increased at 2000 and 10,000 mg/m3

 for gd 6-7, significantly reduced at 20,000 mg/m3 for gd 

7-8, and significantly reduced at 20,000 and 30,000 mg/m3 for gd 8-9. Feed consumption (in 

g/day) was also significantly reduced at 30,000 mg/m3 for gd 10-11, significantly increased at 

10,000 mg/m3

 for gd 12-13, and significantly increased at 30,000 mg/m3 for gd 13-14. Feed 

consumption in g/day was equivalent across all groups for gd 9-10, 11-12, 14-15, 15-16, 16-17 

(postexposure period, Groups 1-4), gd 5-10 (exposure period only for Group 5, 30,000 mg/m3

), 

gd 5-16 (exposure period for Groups 1-4), gd 10-17 (postexposure period for Group 5), and gd 

0-17 (gestational period) (Table 4). None of these feed consumption changes are considered 

adverse or treatment related; all are likely incidental. 

 Maternal feed consumption (in g/kg body weight/day) was significantly reduced at 

20,000 mg/m3

 for gd 0-5 (pre-exposure period), significantly increased at 10,000 mg/m3 for 

gd 5-6, significantly increased at 2000 and 10,000 mg/m3 for gd 6-7, significantly reduced at 

20,000 mg/m3

 for gd 7-8, 8-9, 9-10, and 11-12, significantly reduced at 30,000 mg/m3 for gd 8-9, 

10-11, and 5-10 (exposure period for Group 5), and significantly increased at 30,000 mg/m3

 for 

gd 13-14. There were no differences across groups for feed consumption (in g/kg/day) for gd 
RTI-909; Project 0209189.000 Final Report 

19

12-13, 14-15, 15-16, 16-17 (postexposure period for Groups 1-4), gd 5-16 (exposure period, 

Groups 1-4), gd 10-17 (postexposure period for Group 5), and gd 0-17 (gestation period) (Table 

4). Changes in relative feed consumption at 20,000 and 30,000 mg/m3

 during the exposure 

period were likely due to the processes for inhalation exposure; after the exposure period, there 

were essentially no effects on feed consumption. 

 At scheduled necropsy on gd 17, maternal absolute gravid uterine weight, paired adrenal 

gland weight, and paired kidney weight were unaffected across all groups. Maternal absolute 

liver weight was equivalent across 0, 2000, 20,000, and 30,000 mg/m3 and was significantly 

increased (11%; p<0.05) at 10,000 mg/m3

. Maternal paired adrenal gland and paired kidney 

weights (relative to terminal body weights) were equivalent across all groups. Relative (to 

terminal body weight) maternal liver weight was significantly increased in a concentrationrelated manner at 2000 (6%; p<0.01), 10,000 (11%; p<0.001), and 20,000 (11%; p<0.001) 

mg/m3, likely due to induction of metabolizing enzymes detected in dams exposed through gd 16 

(observed in Groups 1-4, with exposures ending on gd 16); relative liver weight was unaffected 

at 30,000 mg/m3, with exposures ending on gd 10, most likely due to down regulation of 

metabolizing enzymes postexposure (Conney, 1967) (Table 5). 

Uterine and Embryofetal Findings

Tables 6-8, Appendix II 

 For all pregnant females, there were no effects across groups for any reproductive 

parameter, including no statistically significant effects on the number of ovarian corpora 

lutea/dam, number of uterine implantation sites/litter, percent preimplantation loss/litter, number 

(and %) of resorptions/litter, number (and %) of litters with resorptions, number (and %) of late 

fetal deaths/litter, number (and %) of litters with late fetal deaths, number (and %) of nonlive 

(late fetal deaths plus resorptions) implants/litter, number (and %) of litters with nonlive 

implants, number (and %) of litters with 100% nonlive implants (fully resorbed), number (or %) 

of adversely affected (nonlive plus malformed) implants/litter, and number (and %) of litters 

with adversely affected implants. There were 0, 1, 0, 2, and 3 fully resorbed litters (100% 

resorptions) at 0, 2000, 10,000, 20,000, and 30,000 mg/m3

, respectively. These findings did not 

differ statistically across groups but might indicate maternal stress at 20,000 and 30,000 mg/m3

, 
RTI-909; Project 0209189.000 Final Report 

20

with slightly increased numbers of fully resorbed litters (full litter losses are almost always 

ascribed to effects on the maternal animal) (Table 6). 

 For live litters, there were no effects across groups for the number of live fetuses/litter, 

percent male fetuses/litter, number of male or female fetuses/litter, or for average fetal body 

weight/litter for all fetuses or separately by sex (Table 6). 

 Summary and statistical analysis of fetal external malformations and variations are 

presented in Table 7. Presentation of fetal external malformations and variations by defect type 

is in Table 8. The number of fetuses (litters) examined were 276 (23), 236 (21), 225 (19), 

252 (20), and 407 (33) at 0, 2000, 10,000, 20,000, and 30,000 mg/m3

, respectively. There were 

no statistically significant differences across groups for any of the parameters evaluated. These 

parameters included the number and percentage of fetuses with external malformations per litter 

(total and separately by sex), the number and percentage of fetuses (pooled by group) with 

external malformations, and of litters with at least 1 fetus with external malformations. Also, 

there were no differences across groups for the same parameters as above for fetal external 

variations. There were fetal external malformations and variations observed at low incidence in 

all 5 groups (Table 7). 

 The fetal external malformations included encephalocele in 1 fetus in 1 litter (Dam No. 

2819, Implant No. 5) at 2000 mg/m3

, cleft palate in 2 fetuses (2 litters), 1(1), 1(1), 1(1), and 7(4) 

at 0, 2000, 10,000, 20,000, and 30,000 mg/m3 respectively, and gastroschisis in 1 fetus in 1 litter 

(Dam No. 5810, Implant No. 7) at 30,000 mg/m3

. This apparent (nonstatistically significant) 

increase in the fetal (and litter) incidence of cleft palate at 30,000 mg/m3

 may be indirect 

evidence of maternal stress during exposures at this high concentration (see Discussion below). 

The fetal external variations included abnormal rugae in the midline of the palate in 

1 fetus in 1 litter each at 10,000 (Dam No. 3822, Implant No. 15) and 20,000 mg/m3

 (Dam No. 

4822, Implant No. 3), not cleft palate, and hematomas at various locations (face, head, neck, and 

shoulder) in 4 fetuses (in 4 litters) at 0 and 2000 mg/m3, in 1 fetus (in 1 litter) at 10,000 mg/m3, 

in 2 fetuses (in 2 litters) at 20,000 mg/m3, and in no fetuses at 30,000 mg/m3 (Table 8). None of 

these external variations are considered related to treatment or exposure concentrations. 

The historical control data for 288 litters of CD-1 mice at RTI International for 

governmental clients from 1997-2002 are presented in Table 9. 
RTI-909; Project 0209189.000 Final Report 

21

DISCUSSION 

 This study was designed and performed: 

1. To confirm or refute the fetal malformation finding of ectopia cordis observed in 

1 fetus at 2000 mg/m3 and in 2 fetuses (in the same litter) at 10,000 mg/m3 in the 

previous developmental toxicity study on this test material in CD-1® mice 

(EMBSI, 2009b); 

2. To confirm or refute the fetal malformation finding of gastroschisis observed in 1 

fetus at 10,000 mg/m3 (but not at 2000 or 20,000 mg/m3) in the previous 

developmental toxicity study at EMBSI (2009b) on this test material in CD-1® 

mice; 

3. To extend the test atmospheric concentration range from 0, 2000, 10,000, and 

20,000 mg/m3 on gd 5 through 16 employed previously (EMBSI, 2009b), to 0, 

2000, 10,000, 20,000, and 30,000 mg/m3

 (the last concentration at 75% of the 

lower explosive limit), with daily exposures on gd 5 through 16 for the 0-20,000 

mg/m3

 groups and on gd 5 through 10 for the 30,000 mg/m3 group. This last 

gestation interval was included to encompass the time of embryonic ventral wall 

closure, the failure of which is likely responsible for both ectopia cordis and 

gastroschisis. There were 23 plug-positive females/group at 0-20,000 mg/m3

 and 

38 plug-positive females at 30,000 mg/m3 to improve the possibility of detection 

of these rare fetal malformations. 

 There were no apparent treatment-related effects on maternal body weights or weight 

gains and no consistent treatment- or concentration-related effects on maternal feed 

consumption. The treatment-related increases in absolute (at 10,000 mg/m3

) and relative (at 

2000, 10,000, and 20,000 mg/m3) maternal liver weights are most likely due to the induction of 

hepatic metabolizing enzymes, with the concomitant increase in liver weight (Conney, 1967). 

This is not considered maternal toxicity, per se, but an adaptive metabolic response to exposure 

to a xenobiotic. The absence of an increased liver weight at 30,000 mg/m3 might reflect the 7-

day interval between the end of treatment and necropsy of animals in this group. It seems likely, 

given the increases seen in the other test-substance-treated groups, that liver weights were 

initially increased in all treatment groups. 
RTI-909; Project 0209189.000 Final Report 

22

Terminal maternal adrenal gland weights were not changed across groups, although the 

current thinking is that there may be increased maternal production of corticosterone (shown to 

cause fetal cleft palate; Hemm et al., 1977; Pradat et al., 2003; Senda et al., 2005; Carmichael et 

al., 2007) in response to the stress of moving the animals in and out of chambers in all groups 

and in the high “dose” group also from the stress of the narcotic/lethargic effect of MTBE at this 

concentration (see Bevan et al., 1997a,b). It is possible (if not probable) that the adrenal glands 

of the dams exposed to 30,000 mg/m3

 on gd 5-10 were producing increased corticosterone (with 

temporary glandular enlargement) during the exposure period, with resolution of increased 

hormone output and glandular changes by scheduled termination on gd 17. Interestingly, 

lethargy was observed in the females at 30,000 mg/m3

 in the range-finding study but was not 

documented in this study during the daily exposures; it is likely the admittedly subjective effect 

was present in this study since it was present in the range-finding study at the same exposure 

concentration and duration. Clinical observations of the dams did indicate treatment-related 

findings, i.e., labored breathing only at 20,000 and 30,000 mg/m3 postexposure on gd 9 and 10, 

respectively, in 1 female in each group, and lacrimation in 1 female on gd 6 at 20,000 mg/m3

 and 

in 3 females on gd 5 and 6 at 30,000 mg/m3, early in the exposure period. 

 The CD-1® (Swiss) mice used in the previous study (EMBSI, 2009b) were from the 

Charles River, Portage, MI, facility; the CD-1® (Swiss) mice used in the current study were 

from the Charles River, Raleigh, NC, facility, because RTI International has a historical control 

database for developmental toxicity studies on this mouse strain from this source, and to 

preclude the possibility that the fetal findings from the EMBSI study were due to a different 

spontaneous rate of these two fetal malformations in the Portage colony (due to founder effects, 

genetic drift, etc.). Females like the pseudohermaphroditic adult female at 10,000 mg/m3

(removed from study) have been observed at very low incidence in other studies with this mouse 

strain at RTI International from the Charles River, Raleigh, NC, facility. 

1. This study did not confirm the presence of ectopia cordis in any mouse fetus at 

any exposure concentration out of a total 122 litters and 1396 fetuses. In the 

absence of a clear dose-response pattern to this finding in the EMBSI (2009b) 

study and the total absence of this finding in the present study, it is the Study 

Director’s opinion that it is appropriate (and prudent) to conclude that this fetal 

finding is likely not related to maternal exposure to the test material. 
RTI-909; Project 0209189.000 Final Report 

23

2. This study did not confirm the presence of gastroschisis in fetuses at 2000, 

10,000, or 20,000 mg/m3

; it was also not found at 2000 or 20,000 mg/m3 at 

EMBSI (2009b). One fetus (out of 407) did exhibit gastroschisis at 30,000 mg/m3

in the present study. This fetus (No. 6 female) was from Female No. 5810; her 

litter included 15 implants and 14 live fetuses. In her litter, fetus No. 5 female 

and fetus No. 12 male exhibited cleft palates, and fetus No. 6 female had cleft 

palate as well as gastroschisis. In this group at 30,000 mg/m3

, there were 7 

fetuses in 4 litters with cleft palate (greater incidence relative to other 4 groups, 

but not statistically significantly different), with 3 of them in this index litter. The 

body weight of the single female fetus with gastroschisis and cleft palate was 

much lower (0.6057 g) than the body weights of the remaining fetuses in the 

litter: females 0.8034-0.9768 g; males 0.8406-0.8893 g (Table A-4 in Appendix 

II). Her body weight was also much lower than the mean female fetal body 

weight/litter for this group (1.0141±0.0239 [S.E.M.] g); i.e., she was classified as 

a “runt,” with a body weight below 3 standard deviations (and 3 standard errors) 

from the litter mean by sex in this group (Table 6). Although there is a known 

relationship between fetal body weight and cleft palate (i.e., malformed fetuses 

tend to be lighter at term than normal fetuses; Ryan et al., 1991), there are not yet 

any data on the biological relationship between reduced fetal body weight and 

other malformations (i.e., is it cause and/or effect?). This 30,000 mg/m3 group 

also contained 3 fully resorbed litters (out of 36 pregnant). At 20,000 mg/m3

, 2 

litters were fully resorbed (out of 22 pregnant), and 1 fetus in 1 litter exhibited 

cleft palate (and no incidence of gastroschisis). There were no fully resorbed 

litters at 0 or 10,000 mg/m3

 and only 1 fully resorbed litter at 2000 mg/m3 (Table 

2). Cleft palate was present in 2 fetuses in 2 litters at 0 mg/m3

 and in 1 fetus in 1 

litter each at 2000, 10,000, and 20,000 mg/m3

 (Table 8). The increase in fetal and 

litter incidence of cleft palate and the increase in fully resorbed litters at 30,000 

mg/m3 provide circumstantial evidence for maternal toxicity (i.e., stress from the 

exposure procedures, per se, and from a very high level of G/MTBE, resulting in 

additional stress and excessive corticosteroid production known to cause cleft 

palate; Hemm et al., 1977; Pradat et al., 2003; Senda et al., 2005; Carmichael et 
RTI-909; Project 0209189.000 Final Report 

24

al., 2007). Maternal toxicity (stress) is also known to cause full litter resorptions; 

it is ascribed to the dam, not the conceptuses, and exposure on gd 5-10 

corresponded to periods of early implantation and palatal sensitivities. The 

presence of gastroschisis in 1 fetus at 30,000 mg/m3

 may also indicate a possible 

association with maternal stress and G/MTBE only at this very high atmospheric 

concentration. 

 In the present study, gastroschisis was observed in only 1 fetus, only at 30,000 mg/m3 and 

only in the presence of profound developmental toxicity for that fetus (very low body weight and 

cleft palate). There was also general evidence of toxicity in this group (e.g., lethargy observed in 

dams in the range-finding study at 30,000 mg/m3

) and lower individual maternal body weight 

gain (1.9 g) for Dam No. 5810 with the fetus with gastroschisis, versus the 30,000 mg/m3

 mean 

(3.0 g) and the vehicle control group mean (3.3 g) for weight gain during gd 5-10, the exposure 

period. Historical control data from governmental studies with the Charles River CD-1®

(Swiss) mouse at RTI (Table 9), with 288 litters and 3641 fetuses, indicates no fetuses with 

gastroschisis or ectopia cordis. There were 18 fetuses in 11 control litters (in 6 studies) with cleft 

palate (1 to 4 litters affected/affected study) and 2 fetuses in 2 control litters (1/litter) with 

exencephaly in 2 studies, 1 litter affected/affected study. The absence of gastroschisis in any of 

the 3,641 control CD-1 mouse fetuses in 288 control litters (Table 9) lends support to the 

conclusion that gastroschisis in this study may be treatment related, occurring in a compromised 

fetus at 30,000 mg/m3

 with likely concomitant maternal toxicity (see above and conclusion No. 4 

below). No other historical control data on maternal and fetal findings in the Charles River 

CD-1® mouse could be found in the open literature. 

Neither gastroschisis nor ectopia cordis was observed in CD-1® mouse fetuses from 

mothers exposed to 0, 1000, 4000, or 8000 ppm MTBE by whole-body inhalation (in the 

presence of maternal and embryofetal toxicity at 4000 and 8000 ppm MTBE; Bevan et al., 

1997a), nor was either of these malformations observed in mice exposed to a vapor condensate 

of gasoline as part of this testing program (EMBSI, 2009a). It does not appear that exposure to 

either MTBE or gasoline vapor, at atmospheric concentrations <8000 ppm, causes ectopia cordis 

or gastroschisis in mice. Maternal ataxia, hypoactivity, prostration, labored breathing, and 

lacrimation were observed at 4000 and 8000 ppm MTBE, and the resultant stress was considered 

most likely responsible for (or at least exacerbated) the increased incidence of fetal cleft palate at 
RTI-909; Project 0209189.000 Final Report 

25

8000 ppm. Reduced fetal body weights and concomitant reduced fetal skeletal ossification were 

also observed at 4000 and 8000 ppm MTBE vapor, with 4 fully resorbed litters at 8000 ppm 

MTBE (Bevan et al., 1997a). Neither gastroschisis nor ectopia cordis was observed in CD® rat 

offspring in a 2-generation study of inhaled MTBE at 400, 3000, or 8000 ppm (Bevan et al., 

1997b) or in rabbit fetuses from does exposed to 1000, 4000, or 8000 ppm MTBE in a 

developmental toxicity study (Bevan et al., 1997a). Ventral closure defects were also not 

observed in rat reproductive and developmental toxicity studies conducted with gasoline vapor 

condensate or G/MTBE (EMBSI, 2009a,b; Huntingdon Life Sciences, Inc., 2009a,b), nor with 

light ends of gasoline (Roberts et. al., 2001), nor in the mouse developmental toxicity study 

conducted with gasoline vapor condensate (EMBSI, 2009a). 

 The incidence of fetal cleft palate in the EMBSI study was only 1 fetus (in 1 litter), and 

only at 20,000 mg/m3

 (that study’s highest concentration). In the present study, cleft palate was 

observed in all 5 groups, including the air control group (2 fetuses in 2 litters), at 2000- 

20,000 mg/m3

 (1 fetus in 1 litter in each group) and at 30,000 mg/m3 (7 fetuses in 4 litters). The 

increased incidence of cleft palate observed at 30,000 mg/m3

, although not statistically 

significantly different from the control value, was considered to be biologically relevant. Cleft 

palate in fetal mice is inducible by increased corticosterone levels in the dam (and presumably 

transported to the fetuses; Carmichael et al., 2007; Senda et al., 2005; Pradat et al., 2003; Hemm 

et al., 1997). Maternal increased corticosterone levels may be attributed to increased maternal 

stress from inhalation exposures, per se (moving dams into and out of chambers, exposure to 

dynamic air flows, no feed or water during exposure periods, no solid flooring in exposure cages, 

etc.), and from test materials at anesthetic concentrations. In fact, maternal inhalation of MTBE 

has been shown to produce cleft palates in fetuses from CD-1 mouse dams which exhibited 

lethargy and apparent unconsciousness (Bevan et al., 1997a). Maternal lethargy during 

exposures was also observed by HLS staff during the daily exposure periods of G/MTBE at 

30,000 mg/m3

 in the range-finding study at HLS (it was not noted by HLS staff during the daily 

exposure periods at any concentration in this definitive study). Therefore, the presence of fetal 

cleft palate in all groups (including the control group) was not unexpected, and the increased 

incidence at 30,000 mg/m3

 (from both inhalation procedures, per se, and the anesthetic qualities 

of the MTBE in the G/MTBE at this atmospheric concentration) was also anticipated. The 

increased cleft palate incidence at 30,000 mg/m3

 is interpreted as most likely secondary to 
RTI-909; Project 0209189.000 Final Report 

26

maternal stress effects. Maternal stress may have also played a role in the single case of 

gastroschisis in a vulnerable, compromised fetus developing in a dam exposed to anesthetic 

levels of MTBE. Since the maternal exposures to 30,000 mg/m3

 were from gd 5-10, it is highly 

likely that any indications of maternal stress or other toxicity (e.g., increased adrenal weights) 

would have resolved during the postexposure period (gd 10-17) and were therefore not present at 

scheduled necropsy on gd 17. 

CONCLUSIONS 

 In conclusion, this study has demonstrated the following: 

1. No confirmation of fetal ectopia cordis at any test atmospheric concentration 

employed; 

2. No confirmation of fetal gastroschisis at 0-20,000 mg/m3

; 

3. One fetus (out of 407 fetuses, 0.24%) in one litter (out of 33 litters with live 

fetuses, 3.03%) exhibited gastroschisis at 30,000 mg/m3

; this female fetus had 

very low body weight (designated a “runt”), also exhibited cleft palate, and was 

clearly compromised. The single incidence of gastroschisis and the increased 

incidence of cleft palate in this group may both be related to fetal toxicity, 

secondary to maternal stress, only at 30,000 mg/m3. 

4. Fetal cleft palate was present at a low incidence (1-2 fetuses/group) at 0-20,000 

mg/m3, with increased incidences (7 fetuses in 4 litters) at 30,000 mg/m3, likely 

due to greater maternal stress from the anesthetic qualities of the test atmosphere 

at this concentration. See above for discussion on maternal stress causing 

elevated corticosteroids, which in turn cause offspring cleft palate. Since the 

dams at 30,000 mg/m3

 were exposed only on gd 5-10, the offspring palates would 

have been affected (Hemm et al., 1977; Pradat et al., 2003; Senda et al., 2005; 

Carmichael et al., 2007), but any elevated corticosteroid levels (and any effects on 

adrenal gland weights) would likely have resolved by gd 17 at the time of 

necropsy. Relatively minor maternal treatment-related clinical signs of distress 

were observed at 20,000 and 30,000 mg/m3

 in this study, with greater maternal 

clinical signs observed at 30,000 mg/m3

 in the range-finding study. The increased 

incidence of fetal cleft palate and the presence of gastroschisis in 1 fetus in this 
RTI-909; Project 0209189.000 Final Report 

27

group, in this study, may indicate effects on compromised fetuses in the presence 

of maternal stress (toxicity). The presence of gastroschisis at 30,000 mg/m3

 and 

its absence from all available CD-1 historical control databases lends some 

support to the possible conclusion that the presence of 1 fetus with gastroschisis 

may have been treatment related, secondary to maternal stress. 

5. Therefore, in the Study Director’s opinion, maternal exposure to the test chemical 

at 30,000 mg/m3, an extremely high atmospheric concentration, in the presence of 

fetal and demonstrable maternal toxicity during the embryonic period of ventral 

body wall closure, may have resulted in a very low incidence of gastroschisis (1 

out of 407 fetuses, 0.24%; 1 out of 33 litters with live fetuses, 3.03%) in 

vulnerable mouse fetuses in the highest concentration group. The one affected 

fetus also exhibited reduced body weight and cleft palate. With lower fetal and 

maternal toxicity at 20,000 mg/m3 and below, there was no incidence of 

gastroschisis. The absence of any mouse fetus with gastroschisis in the 

performing laboratory’s historical control database lends some support to the 

possible conclusion that the single case of gastroschisis at a very high atmosphere 

of G/MTBE (30,000 mg/m3) in this study may have been treatment related. Since 

the one affected female fetus at 30,000 mg/m3 was also very small (a “runt”) and 

also exhibited cleft palate, her malformation findings may have been caused by 

(or exacerbated by) maternal exposure to G/MTBE. Alternatively, the fetal 

effects may have been caused by (or exacerbated by) maternal toxicity (stress) or 

may have been a spontaneous fetal malformation. 

 Under the conditions of this study, the NOAELs for maternal and developmental 

toxicity, based on the maternal effects observed at 20,000 and 30,000 mg/m3

 and the 

developmental effects observed at 30,000 mg/m3

, were determined by the Study Director 

to be 10,000 mg/m3 for maternal toxicity and 20,000 mg/m3 for developmental toxicity. 
RTI-909; Project 0209189.000 Final Report 

28

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32

LIST OF PROTOCOL DEVIATIONS

Study: Mi04-HLS2 Master Protocol No.: RTI-909 HLS Study Code: 04-4263 

HLS

1. Due to technician error, food left weights were recorded for the Exposure Day 12-13 

interval, but food fed weights for the Exposure Day 13-14 interval were not entered into 

the computer system for Animal Nos. 1805, 1806, 1807, 1808, 1809, 1810, 1811, 1812, 

1814, 1815, 1816, 1818, 1819, 1820, 1823, 2804, 2806, 2808, 2814, 2815, 2817, 2818, 

2819, 2821, 2822, and 2823. Since the feeders for these animals were returned to the cages 

after obtaining the food left weights and did not need to be changed, a series of edits was 

performed which provided a food fed weight equivalent to the food left weight. 

2. Due to the unexpectedly extended mating period, only 130 mice were placed on test rather 

than 140. This resulted in the following group sizes: Group 1-4 had 23 mice and Group 5 

had 38 mice. 

3. The group means for MIRAN sampling were outside of the stated protocol range of ± 10% 

on Exposure Days 6, 9, 16 (Group 2), Exposure Days 16 and 19 (Group 3), and Exposure 

Day 2 and 16 (Group 4). 

4. Individual MIRAN samples were outside the protocol specified range of ± 10% for the 

following Sample Nos.: 2001, 2002, 2020, 2021, 2022, 2032, 2034, 2035, 2036, 2037, 

2044, 2052, 2063, 2064, 3061, 3062, 3063, 3064, 3065, 3066, 3077, 3078, 4001, 4004, 

4005, 4406, 4016, 4024, 4063, 4064, 4070, 5001, 5005 and 5025. Chamber concentration 

values were confirmed as needed in accordance with Testing Facility SOP. 

5. Due to technician oversight, a Nestlet® was given to Animal No. 5838 during the morning 

of Exposure Day 16 (removed after a total of 37 minutes) and then again in the afternoon. 

The protocol specifications were for afternoon only. 

6. Due to technician oversight, animals in Groups 1-4 chambers and Group 5 chamber were 

not rotated on Exposure Days 11 and 13, respectively. 

7. At RTI’s request, with the Sponsor’s approval, nonpregnant females were sacrificed and 

examined macroscopically in order to determine their actual state of pregnancy, although 

not required by protocol. 

8. Due to a communication error with the Sponsor’s Representative, Group 5 dams were 

removed from their cages with Nestlets® and inserts only from GD 14-16 and placed into 

cages without Nestlets® and inserts to simulate the Groups 1-4 exposure regimen. Per 

intent of Sponsor, the Group 5 dams should have been removed from their cages with 

Nestlets® and inserts from GD 10-16 and placed into cages without Nestlets® and inserts 
RTI-909; Project 0209189.000 Final Report 

33

to simulate the cage environment of the females in Groups 1-4 during the remaining 

exposure on gd 16. 

9. Due to the HLS Principal Investigator’s oversight, Protocol Amendment No. 2 was signed 

by one IACUC member instead of two, as designated by the protocol. 

In the Study Director’s professional opinion, these protocol deviations did not affect the study 

design, performance, or interpretation and are presented for completeness. 
RTI-909; Project 0209189.000 Final Report 

34

Table 1. Analysis of Test Atmospheres (page 1 of 1) 

 Target Concentrations (mg/m3

) 

 0 2000 10,000 20,000 30,000 

Mean analytical 

concentration ± SD 

(% of target)a

0 ± 0b

 

(NA) 

2074 ± 248 

(103.7) 

9925 ± 688 

(99.25) 

20,342 ± 1815 

(101.7) 

29,250 ± 1480 

(97.5) 

Particle Size Determination:c 

 MMAD (μm) 2.179 5.699 9.319 3.845 1.144 

 GSD 1.676 2.117 2.071 1.955 2.910 

 TMC (mg/m3

) 2.56 x 10-2 5.05 x 10-3 3.41 x 10-3 1.47 x 10-3 1.54 x 10-2

Mean temperature (°C ± SD)d 20.3 ± 0.9 20.8 ± 1.2 21.5 ± 0.9 20.7 ±0.9 20.7 ±0.8 

Mean relative humidity 

(% ± SD)d

31.2 ± 4.9 32.0 ± 7.1 28.6 ± 4.2 28.4 ± 4.1 27.6 ± 4.7 

a

 Mean of 4 assays/chamber/day (20 days for Group 1, 18 days for Group 2, 22 days for Group 3, 

19 days for Group 4, and 12 days for Group 5) measured by infrared spectroscopy 

b

 Estimated limit of quantification (LOQ) = 433 mg/m3 (Appendix I) 

c

 Measured 1 time/chamber 

d

 Measured 13 times/chamber/day 

SD = Standard deviation 

MMAD = mass median aerodynamic diameter 

GSD = geometric standard deviation 

TMC = total mass concentration (measure of aerosol concentration) 
RTI-909; Project 0209189.000 Final Report 

35

Table 2. Summary and Statistical Analysis of the Maternal Body Weights and Body Weight Changes 

(page 1 of 6) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10

 0 2000 10,000 20,000 30,000 

Subjects (No. Dams) 

No. on Study 23 23 23 23 38 

No. Removed 0 0 1a 0 0 

No. Dead or Euthanized 0 0 0 0 0 

No. Nonpregnant 0 1 3 1 2 

No. (%) Pregnant at 

Scheduled Sacrifice 

23 (100.0) 22 (95.7) 19 (86.4) 22 (95.7) 36 (94.7) 

No. (%) with 100% 

Resorptions 

0 (0.0) 1 (4.5) 0 (0.0) 2 (9.1) 3 (8.3) 

Maternal Body Weight (gd 0) (g)b 

26.7 27.2 27.0 27.3 27.5 

 + 0.4 + 0.3 + 0.3 + 0.3 + 0.2 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight (gd 5) (g)b 

27.6 28.4 27.8 28.5 28.3 

 + 0.4 + 0.4 + 0.4 + 0.3 + 0.3 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight (gd 6) (g)b 

 28.2 29.1 28.7 29.0 28.8 

 + 0.4 + 0.4 + 0.4 + 0.3 + 0.3 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight (gd 7) (g)b 

 28.7 29.7 29.1 29.6 29.3 

 + 0.4 + 0.4 + 0.4 + 0.3 + 0.3 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight (gd 8) (g)b 

29.2 30.2 29.7 30.0 29.8 

 + 0.4 + 0.4 + 0.4 + 0.3 + 0.3 

 N=23 N=22 N=19 N=22 N=36 
RTI-909; Project 0209189.000 Final Report 

36

Table 2. Summary and Statistical Analysis of the Maternal Body Weights and Body Weight Changes 

(page 2 of 6) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

Maternal Body Weight (gd 9) (g)b 

29.7 30.6 30.3 30.6 30.4 

 + 0.4 + 0.5 + 0.5 + 0.4 + 0.4 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight (gd 10) (g)b 

 30.9 31.8 31.6 31.5 31.3 

 + 0.5 + 0.6 + 0.5 + 0.4 + 0.4 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight (gd 11) (g)b 

 32.8 33.9 33.6 33.2 33.0 

 + 0.5 + 0.6 + 0.6 + 0.5 + 0.5 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight (gd 12) (g)b 

 34.9 35.8 35.5 35.1 35.3 

 + 0.5 + 0.8 + 0.5 + 0.6 + 0.5 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight (gd 13) (g)b 

36.9 37.2 37.3 36.7 37.4 

 + 0.5 + 0.9 + 0.6 + 0.7 + 0.6 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight (gd 14) (g)b 

 39.2 39.2 39.4 38.7 39.7 

 + 0.6 + 1.0 + 0.6 + 0.9 + 0.7 

 N=23 N=22 N=19 N=22 N=36 
RTI-909; Project 0209189.000 Final Report 

37

Table 2. Summary and Statistical Analysis of the Maternal Body Weights and Body Weight Changes 

(page 3 of 6) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

Maternal Body Weight (gd 15) (g)b 

 42.0 42.0 42.2 41.2 42.4 

 + 0.6 + 1.1 + 0.7 + 1.0 + 0.9 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight (gd 16) (g)b 

 45.2 45.1 45.3 44.0 45.2 

 + 0.7 + 1.4 + 0.7 + 1.2 + 1.1 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight (gd 17) (g)b 

 48.4 48.0 48.3 46.7 48.3 

 + 0.7 + 1.5 + 0.8 + 1.4 + 1.2 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight (gd 17 at 

sacrifice) (g)b

 

 47.14 46.71 47.52 45.91 47.44 

 + 0.73 + 1.50 + 0.79 + 1.43 + 1.18 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight Change (gd 0 

to 5) (g)b

 

 0.8 1.2 0.8 1.2 0.8 

 + 0.2 + 0.3 + 0.3 + 0.2 + 0.2 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight Change (gd 5 

to 6) (g)b

 

 0.6 0.7 0.9 0.5 0.5 

 + 0.1 + 0.1 + 0.2 + 0.1 + 0.1 

 N=23 N=22 N=19 N=22 N=36 
RTI-909; Project 0209189.000 Final Report 

38

Table 2. Summary and Statistical Analysis of the Maternal Body Weights and Body Weight Changes 

(page 4 of 6) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

Maternal Body Weight Change 

(gd 6 to 7) (g)b

 

# 0.6 0.6 0.5 0.6 0.5 

 + 0.1 + 0.1 + 0.1 + 0.1 + 0.1 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight Change 

(gd 7 to 8) (g)b

 

 0.5 0.5 0.6 0.4 0.5 

 + 0.1 + 0.1 + 0.1 + 0.1 + 0.1 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight Change 

(gd 8 to 9) (g)b

 

 0.5 0.4 0.6 0.5 0.6 

 + 0.1 + 0.1 + 0.1 + 0.1 + 0.1 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight Change 

(gd 9 to 10) (g)b

 

1.2 1.2 1.3 0.9 0.9 

 + 0.1 § + 0.1 + 0.2 + 0.1 + 0.1 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight Change 

(gd 10 to 11) (g)b

 

1.9 2.0 2.0 1.7 1.7 

 + 0.1 + 0.2 + 0.1 + 0.2 + 0.1 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight Change 

(gd 11 to 12) (g)b

 

2.1 1.9 1.8 2.0 2.3 

 + 0.1 § + 0.2 + 0.1 + 0.2 + 0.1 

 N=23 N=22 N=19 N=22 N=36 
RTI-909; Project 0209189.000 Final Report 

39

Table 2. Summary and Statistical Analysis of the Maternal Body Weights and Body Weight Changes 

(page 5 of 6) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

Maternal Body Weight Change 

(gd 12 to 13) (g)b

 

 2.1 ‡‡ 1.4 ** 1.9 1.5 * 2.0 

 + 0.1 + 0.2 + 0.1 + 0.2 + 0.1 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight Change 

(gd 13 to 14) (g)b

 

2.3 2.0 2.1 2.0 2.3 

 + 0.1 + 0.2 + 0.1 + 0.2 + 0.2 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight Change 

(gd 14 to 15) (g)b

 

2.8 2.8 2.8 2.5 2.7 

 + 0.1 + 0.2 + 0.1 + 0.2 + 0.3 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight Change 

(gd 15 to 16) (g)b

 

3.2 3.1 3.0 2.8 2.9 

 + 0.2 + 0.2 + 0.1 + 0.3 + 0.2 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight Change 

(gd 16 to 17) (g)b

 

3.2 2.9 3.1 2.7 3.1 

 + 0.2 + 0.2 + 0.1 + 0.2 + 0.1 

 N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight Change 

(gd 5 to 10) (g)b,c

 

 3.3 3.0 

 + 0.2 + 0.2 

 N=23 N=36 

Maternal Body Weight Change 

(gd 5 to 16) (g)b,d

 

 17.6 16.7 17.5 15.5 

 + 0.4 + 1.2 + 0.5 + 1.2 

N=23 N=22 N=19 N=22 
RTI-909; Project 0209189.000 Final Report 

40

Table 2. Summary and Statistical Analysis of the Maternal Body Weights and Body Weight Changes 

(page 6 of 6) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10

 0 2000 10,000 20,000 30,000 

Maternal Body Weight Change (gd 10 to 

17) (g)b,c

 

17.5 17.0 

 + 0.4 + 0.9 

N=23 N=36 

Maternal Body Weight 

Change (gestation) (g)b

 

 20.4 19.6 20.5 18.6 20.0 

 + 0.6 + 1.3 + 0.7 + 1.5 + 1.1 

N=23 N=22 N=19 N=22 N=36 

Maternal Body Weight 

Change (corrected) (g)b,e

 

 3.14 3.98 3.95 2.88 3.20 

 + 0.25 + 0.44 + 0.51 + 0.38 + 0.32 

 N=23 N=22 N=19 N=22 N=36 

aFemale 3814 was removed from study due to a pre-existing condition. At necropsy she was found to 

have an undescended testis on the right and seminal vesicles and prostate to the right of the vagina and 

cervix. 

bIncludes all pregnant dams until terminal sacrifice on gestational day 17. Reported as the mean +

S.E.M.; gd=gestational day. 

cThis endpoint was only calculated for the 0 and 30,000 mg/m3 dose groups. 

dThis endpoint was only calculated for the 0, 2000, 10,000, and 20,000 mg/m3 dose groups. 

eWeight change during gestation (gestational day 17 sacrifice weight minus gestational day 0 weight) 

minus gravid uterine weight. 

#Levene’s Test for homogeneity of variances was significant (p<0.05); therefore, robust regression 

methods were used to test all treatment effects. 

‡‡p<0.01; ANOVA Test. 

§p<0.05; Test for Linear Trend.

*p<0.05; Dunnett’s Test.

**p<0.01; Dunnett’s Test. 
RTI-909; Project 0209189.000 Final Report 

41

 Table 3. Summary of the Maternal Clinical Observations (page 1 of 2) 

A. Clinical Observations Summarized by Group 

Gasoline MTBE Vapor Condensate 

(mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 

5-10 

Observation 0 2000 10,000 20,000 30,000 

Alopecia: extremities/snout, moderate 1 

Eye: enophthalmosa, unilateral, left 1 

Labored breathing 1 1 

Lacrimation, bilateral, moderate 1 

Lacrimation, unilateral, moderate 1 2 

Red exudates from anogenital area 1 1 

B. Clinical Observations Summarized by Group, Day, and Time 

 Gasoline MTBE Vapor Condensate (mg/m3, 

inhaled) 

 Dosed gd 5-16 Dosed gd 

5-10 

Dayb Timec Observation 0 2000 10,000 20,000 30,000 

2 Prior Eye: enophthalmos, unilateral, left 1

3 Prior Eye: enophthalmos, unilateral, left 1

4 Prior Eye: enophthalmos, unilateral, left 1

5 Prior Eye: enophthalmos, unilateral, left 1

 Post Alopecia: extremities/snout, moderate 1 

 Eye: enophthalmos, unilateral, left 1

 Lacrimation, unilateral, moderate 1

6 Prior Alopecia: extremities/snout, moderate 1 

 Eye: enophthalmos, unilateral, left 1

 Post Alopecia: extremities/snout, moderate 1 

 Eye: enophthalmos, unilateral, left 1

 Lacrimation, bilateral, moderate 1

 Lacrimation, unilateral, moderate 1 1

7 Prior Alopecia: extremities/snout, moderate 1 

 Eye: enophthalmos, unilateral, left 1

 Post Alopecia: extremities/snout, moderate 1 

 Eye: enophthalmos, unilateral, left 1
RTI-909; Project 0209189.000 Final Report 

42

Table 3. Summary of the Maternal Clinical Observations (page 2 of 2) 

B. Clinical Observations Summarized by Group, Day, and Time 

 Gasoline MTBE Vapor Condensate 

(mg/m3, inhaled) 

 Dosed gd 5-16 Dosed gd 

5-10 

Dayb Timec Observation 0 2000 10,000 20,000 30,000 

8 Prior Alopecia: extremities/snout, moderate 1 

 Eye: enophthalmos, unilateral, left 1 

 Post Alopecia: extremities/snout, moderate 1 

 Eye: enophthalmos, unilateral, left 1 

9 Prior Alopecia: extremities/snout, moderate 1 

 Eye: enophthalmos, unilateral, left 1 

 Post Alopecia: extremities/snout, moderate 1 

 Eye: enophthalmos, unilateral, left 1 

 Labored breathing 1 

10 Prior Alopecia: extremities/snout, moderate 1 

 Eye: enophthalmos, unilateral, left 1 

 Post Alopecia: extremities/snout, moderate 1 

 Eye: enophthalmos, unilateral, left 1 

 Labored breathing 1 

11 Prior Alopecia: extremities/snout, moderate 1 

 Eye: enophthalmos, unilateral, left 1 

 Post Alopecia: extremities/snout, moderate 1 

 Red exudates from anogenital area 1 

12 Prior Alopecia: extremities/snout, moderate 1 

 Eye: enophthalmos, unilateral, left 1 

 Red exudates from anogenital area 1 

 Post Alopecia: extremities/snout, moderate 1 

13 Prior Eye: enophthalmos, unilateral, left 1 

14 Prior Eye: enophthalmos, unilateral, left 1 

15 Prior Eye: enophthalmos, unilateral, left 1 

16 Prior Eye: enophthalmos, unilateral, left 1 

17 Prior Eye: enophthalmos, unilateral, left 1 

aA sinking of the eyeball into the orbital cavity. 

bGestational day. 

cTime is prior to/post (after) exposures. 
RTI-909; Project 0209189.000 Final Report 

43

Table 4. Summary and Statistical Analysis of the Maternal Feed Consumption (page 1 of 6) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

No. Dams 23 22 19 22 36 

Maternal Feed Consumption 

(gd 0 to 5) (g/day)a

 

# 6.1 ††† 6.5 6.2 5.3 ÞÞ 6.8 

 + 0.2 + 0.4 + 0.4 + 0.2 + 0.4 

N=17b N=18b,c N=11b N=16b,c N=25b,c

Maternal Feed Consumption 

(gd 5 to 6) (g/day)a

 

# 6.1 † 6.7 7.7 Þ 6.2 5.9 

 + 0.3 Ÿ + 0.3 + 0.7 + 0.2 + 0.1 

N=20b,d N=21b N=16b N=21d N=32b,d

Maternal Feed Consumption 

(gd 6 to 7) (g/day)a

 

# 6.1 †† 7.8 Þ 7.7 ÞÞÞ 6.2 6.3 

 + 0.2 + 0.7 + 0.4 + 0.3 + 0.2 

N=18b,d N=19b,c,d N=17b N=17b,d N=32b,c

Maternal Feed Consumption 

(gd 7 to 8) (g/day)a

 

# 7.0 ††† 7.4 8.2 6.2 Þ 6.4 

 + 0.4 ŸŸŸ + 0.3 + 0.7 + 0.2 + 0.2 

N=21d N=21d N=19 N=18b,d N=34c,d

Maternal Feed Consumption 

(gd 8 to 9) (g/day)a

 

# 7.6 ††† 6.8 7.5 6.1 ÞÞ 6.2 ÞÞ

 + 0.5 ŸŸŸ + 0.3 + 0.4 + 0.2 + 0.1 

N=21b N=19c,d N=16b,c N=20b,d N=33b,c

Maternal Feed Consumption 

(gd 9 to 10) (g/day)a

 

 6.7 ‡‡‡ 7.0 7.3 6.1 6.3 

 + 0.2 §§ + 0.3 + 0.2 + 0.2 + 0.1 

 N=23 N=21b N=18b N=20b,c N=35b
RTI-909; Project 0209189.000 Final Report 

44

Table 4. Summary and Statistical Analysis of the Maternal Feed Consumption (page 2 of 6) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

Maternal Feed Consumption (gd 10 to 11) 

(g/day)a

 

# 6.9 ††† 7.6 7.5 6.3 6.2 ÞÞ

 + 0.2 ŸŸŸ + 0.3 + 0.2 + 0.2 + 0.1 

N=19b N=22 N=18b N=20d N=33c,d

Maternal Feed Consumption (gd 11 to 12) 

(g/day)a

 

 7.7 ‡ 7.1 7.7 6.7 7.8 

 + 0.4 + 0.2 + 0.3 + 0.2 + 0.3 

 N=23 N=21b N=18b N=20b,d N=33b,c,d

Maternal Feed Consumption (gd 12 to 13) 

(g/day)a

 

 7.1 ‡‡ 7.3 8.0 * 6.9 7.8 

 + 0.2 + 0.3 + 0.3 + 0.2 + 0.2 

 N=23 N=21c N=19 N=22 N=34c,d

Maternal Feed Consumption (gd 13 to 14) 

(g/day)a

 

 7.3 ‡‡ 7.5 7.9 7.1 8.0 *

 + 0.1 § + 0.3 + 0.2 + 0.3 + 0.2 

 N=23 N=20b,c N=18b N=21b N=36 

Maternal Feed Consumption (gd 14 to 15) 

(g/day)a

 

 7.4 7.4 7.8 7.1 7.6 

 + 0.1 + 0.3 + 0.2 + 0.3 + 0.2 

 N=23 N=21b N=19 N=22 N=36 

Maternal Feed Consumption (gd 15 to 16) 

(g/day)a

 

 7.5 ‡ 7.8 7.9 6.9 7.2 

 + 0.2 § + 0.3 + 0.3 + 0.2 + 0.2 

 N=23 N=22 N=19 N=22 N=35c

Maternal Feed Consumption (gd 16 to 17) 

(g/day)a

 

 7.6 7.4 7.8 7.3 7.5 

 + 0.2 + 0.3 + 0.2 + 0.2 + 0.2 

 N=23 N=22 N=19 N=22 N=35c
RTI-909; Project 0209189.000 Final Report 

45

Table 4. Summary and Statistical Analysis of the Maternal Feed Consumption (page 3 of 6) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

Maternal Feed Consumption (gd 5 to 10) 

(g/day)a,e

 

# 6.9 6.2 

 + 0.4 + 0.1 

N=20f N=28f

Maternal Feed Consumption (gd 5 to 16) 

(g/day)a,g

 

 6.9 7.0 7.7 6.8 

 + 0.2 + 0.3 + 0.3 + 0.3 

N=17f N=14f N=12f N=17f

Maternal Feed Consumption (gd 10 to 17) 

(g/day)a,e

 

 7.3 7.6 

 + 0.2 + 0.2 

N=19f N=31f

Maternal Feed Consumption 

(gd 0 to 17) (g/day)a

 

 6.5 ‡ 6.8 7.0 6.1 6.9 

 + 0.1 + 0.3 + 0.3 + 0.2 + 0.2 

N=14f N=13f N=8f N=14f N=20f

Relative Maternal Feed Consumption (gd 0 

to 5) (g/kg/day)a

 

# 224.8 ††† 230.4 223.1 189.4 ÞÞ 241.5 

 + 10.3 + 11.3 + 13.5 + 5.5 + 14.3 

N=17b N=18b,c N=11b N=16b,c N=25b,c

Relative Maternal Feed Consumption (gd 5 

to 6) (g/kg/day)a

 

# 216.1 † 233.1 270.7 Þ 217.3 207.5 

 + 8.3 Ÿ + 9.7 + 24.6 + 8.9 + 4.6 

N=20b,d N=21b N=16b N=21d N=32b,d
RTI-909; Project 0209189.000 Final Report 

46

Table 4. Summary and Statistical Analysis of the Maternal Feed Consumption (page 4 of 6) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

Relative Maternal Feed Consumption (gd 

6 to 7) (g/kg/day)a

 

# 214.6 †† 266.0 Þ 264.7 ÞÞ 213.3 218.1 

 + 7.6 Ÿ + 22.5 + 14.5 + 8.4 + 7.2 

N=18b,d N=19b,c,d N=17b N=17b,d N=32b,c

Relative Maternal Feed Consumption (gd 

7 to 8) (g/kg/day)a

 

# 242.4 ††† 247.6 275.4 208.1 Þ 216.5 

 + 14.8 ŸŸŸ + 10.4 + 21.8 + 5.9 + 5.3 

N=21d N=21d N=19 N=18b,d N=34c,d

Relative Maternal Feed Consumption (gd 

8 to 9) (g/kg/day)a

 

# 255.3 ††† 224.2 249.3 202.6 ÞÞ 204.2 ÞÞ

 + 17.1 ŸŸŸ + 10.3 + 14.0 + 5.9 + 4.0 

N=21b N=19c,d N=16b,c N=20b,d N=33b,c

Relative Maternal Feed Consumption (gd 

9 to 10) (g/kg/day)a

 

 222.9 ‡‡‡ 225.2 234.9 198.8 * 204.8 

 + 8.4 §§ + 8.7 + 7.6 + 4.7 + 3.4 

 N=23 N=21b N=18b N=20b,c N=35b

Relative Maternal Feed Consumption (gd 

10 to 11) (g/kg/day)a

 

 218.8 ‡‡‡ 229.9 230.3 197.4 193.4 *

 + 10.0 §§§ + 8.3 + 6.9 + 6.4 + 2.8 

N=19b N=22 N=18b N=20d N=33c,d

Relative Maternal Feed Consumption (gd 

11 to 12) (g/kg/day)a

 

 228.1 ‡ 203.7 222.9 197.0 * 230.6 

 + 11.6 + 5.1 + 9.0 + 4.6 + 8.0 

 N=23 N=21b N=18b N=20b,d N=33b,c,d

Relative Maternal Feed Consumption (gd 

12 to 13) (g/kg/day)a

 

 198.3 ‡‡ 198.8 221.2 192.0 213.4 

 + 5.9 + 6.0 + 7.5 + 5.9 + 5.6 

 N=23 N=21c N=19 N=22 N=34c,d
RTI-909; Project 0209189.000 Final Report 

47

Table 4. Summary and Statistical Analysis of the Maternal Feed Consumption (page 5 of 6) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

Relative Maternal Feed Consumption (gd 

13 to 14) (g/kg/day)a

 

 191.7 ‡ 195.8 205.9 189.8 209.4 *

 + 4.2 § + 4.9 + 4.9 + 6.6 + 4.1 

 N=23 N=20b,c N=18b N=21b N=36 

Relative Maternal Feed Consumption (gd 

14 to 15) (g/kg/day)a

 

 182.2 182.8 190.7 177.8 187.3 

 + 4.1 + 4.9 + 5.8 + 4.6 + 5.0 

 N=23 N=21b N=19 N=22 N=36 

Relative Maternal Feed Consumption (gd 

15 to 16) (g/kg/day)a

 

 171.5 ‡‡ 179.0 181.5 162.0 163.6 

 + 3.4 §§ + 4.5 + 6.1 + 3.5 + 2.6 

 N=23 N=22 N=19 N=22 N=35c

Relative Maternal Feed Consumption (gd 

16 to 17) (g/kg/day)a

 

 162.9 160.3 166.1 161.2 159.9 

 + 4.7 + 3.4 + 3.4 + 4.6 + 2.4 

 N=23 N=22 N=19 N=22 N=35c

Relative Maternal Feed Consumption (gd 5 

to 10) (g/kg/day)a,e

 

# 235.6 † 209.5 Þ

 + 12.1 Ÿ + 3.7 

N=20f N=28f

Relative Maternal Feed Consumption (gd 5 

to 16) (g/kg/day)a,g

 

 202.6 206.9 222.0 199.3 

 + 5.7 + 5.3 + 6.7 + 7.0 

N=17f N=14f N=12f N=17f

Relative Maternal Feed Consumption (gd 

10 to 17) (g/kg/day)a,e

 

 189.6 194.5 

 + 4.8 + 3.4 

N=19f N=31f
RTI-909; Project 0209189.000 Final Report 

48

Table 4. Summary and Statistical Analysis of the Maternal Feed Consumption (page 6 of 6) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

Relative Maternal Feed Consumption (gd 0 

to 17) (g/kg/day)a

 

 187.1 197.0 198.2 178.6 194.3 

 + 4.9 + 5.8 + 7.0 + 3.8 + 5.1 

N=14f N=13f N=8f N=14f N=20f

aIncludes all pregnant dams until terminal sacrifice on gestational day 17. Reported as the mean +

S.E.M.; gd = gestational day. 

bDecrease in N is due to one or more feeders spilling, and therefore the feed weight was excluded. 

cDecrease in N is due to the feed being contaminated for one or more animals, and therefore the feed 

weight was excluded. 

dDecrease in N is due to the feed consumption value for one or more animals being a statistical outlier, 

and therefore they were excluded. 

eThis endpoint was only calculated for the 0 and 30,000 mg/m3 dose groups. 

f

Decrease in N is due to interim feed consumption value(s) for one or more dams being missing, and 

therefore the overall feed consumption value could not be calculated. 

gThis endpoint was only calculated for the 0, 2000, 10,000, and 20,000 mg/m3 dose groups. 

#Levene’s Test for homogeneity of variances was significant (p<0.05); therefore, robust regression 

methods were used to test all treatment effects. 

†p<0.05; Wald Chi-square Test for overall treatment effect in robust regression model. 

††p<0.01; Wald Chi-square Test for overall treatment effect in robust regression model. 

†††p<0.001; Wald Chi-square Test for overall treatment effect in robust regression model. 

Ϋp<0.05; Linear trend test in robust regression model. 

ΫΫΫp<0.001; Linear trend test in robust regression model. 

Þp<0.05; Individual t-test for pairwise comparisons to control in robust regression model. 

ÞÞp<0.01; Individual t-test for pairwise comparisons to control in robust regression model. 

ÞÞÞp<0.001; Individual t-test for pairwise comparisons to control in robust regression model. 

‡p<0.05; ANOVA Test. 

‡‡p<0.01; ANOVA Test. 

‡‡‡p<0.001; ANOVA Test. 

§p<0.05; Test for Linear Trend.

§§p<0.01; Test for Linear Trend.

§§§p<0.001; Test for Linear Trend.

*p<0.05; Dunnett’s Test.
RTI-909; Project 0209189.000 Final Report 

49

Table 5. Summary and Statistical Analysis of the Maternal Absolute and Relative Organ Weights 

(page 1 of 2) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10

 0 2000 10,000 20,000 30,000 

Absolute Gravid Uterine 

Weight (g)a

 

17.2900 15.5703 16.5732 15.7215 16.7807 

 + 0.4737 + 1.1217 + 0.3737 + 1.2039 + 0.9127 

N=23 N=22 N=19 N=22 N=36 

Absolute Maternal Liver 

Weight (g)a

 

 2.4511 ‡ 2.5766 2.7247 * 2.6308 2.4253 

 +0.0498 +0.0889 +0.0538 +0.0715 +0.0604 

 N=23 N=22 N=19 N=22 N=36 

Absolute Maternal Paired 

Adrenal Gland Weight (g)a

 

 0.0136 0.0144 0.0132 0.0137 0.0135 

 +0.0006 +0.0007 +0.0004 +0.0005 +0.0003 

N=22b N=22 N=18b N=22 N=36 

Absolute Maternal Paired 

Kidney Weight (g)a

 

 0.4277 0.4454 0.4394 0.4376 0.4311 

 +0.0089 +0.0107 +0.0054 +0.0089 +0.0073 

 N=23 N=22 N=19 N=22 N=36 

Relative Maternal Liver Weight (% 

sacrifice weight)a

 

# 5.1961 ††† 5.5269 ÞÞ 5.7418 ÞÞÞ 5.7610 ÞÞÞ 5.1550 

 + 0.0569 + 0.0865 + 0.0927 + 0.0754 + 0.0939 

N=23 N=22 N=19 N=22 N=36 

Relative Maternal Paired Adrenal Gland Weight (% 

sacrifice weight)a

 

0.0290 0.0314 0.0279 0.0306 0.0297 

 + 0.0014 + 0.0016 + 0.0009 + 0.0017 + 0.0015 

N=22b N=22 N=18b N=22 N=36 

Relative Maternal Paired Kidney Weight 

(% sacrifice weight)a

 

0.9067 0.9783 0.9281 0.9817 0.9345 

 + 0.0109 + 0.0451 + 0.0156 + 0.0496 + 0.0337 

N=23 N=22 N=19 N=22 N=36 
RTI-909; Project 0209189.000 Final Report 

50

Table 5. Summary and Statistical Analysis of the Maternal Absolute and Relative Organ Weights 

(page 2 of 2) 

aIncludes all pregnant dams until terminal sacrifice on gestational day 17. Reported as the mean +

S.E.M.; gd=gestational day. 

bDecrease in N is due to the paired adrenal weight for one animal being a statistical outlier and therefore 

it was excluded. 

#Levene’s Test for homogeneity of variances was significant (p<0.05); therefore, robust regression 

methods were used to test all treatment effects. 

‡p<0.05; ANOVA Test. 

*p<0.05; Dunnett’s Test.

†††p<0.001; Wald Chi-square Test for overall treatment effect in robust regression model. 

ÞÞp<0.01; Individual t-test for pairwise comparisons to control in robust regression model. 

ÞÞÞp<0.001; Individual t-test for pairwise comparisons to control in robust regression model. 
RTI-909; Project 0209189.000 Final Report 

51

Table 6. Summary and Statistical Analysis of Ovarian Corpora Lutea, Uterine Contents, Live Fetal Sex 

and Live Fetal Body Weight (page 1 of 4) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

ALL LITTERSa: 23 22 19 22 36 

No. Corpora Lutea per Damb 

12.96 12.18 12.78 13.18 13.19 

 + 0.38 + 0.57 + 0.36 + 0.56 + 0.47 

 N=23 N=22 N=18c N=22 N=36 

No. Implantation Sites per 

Litterb

 

12.74 12.00 12.68 13.23 12.89 

 + 0.35 + 0.61 + 0.33 + 0.46 + 0.37 

 N=23 N=22 N=19 N=22 N=36 

%Preimplantation Loss per 

Litterb

 

2.06 5.99 3.93 2.61 4.81 

 + 0.93 + 3.74 + 1.52 + 0.99 + 1.24 

 N=23 N=22 N=18c N=22 N=36 

No. Resorptions per Litterb 

0.61 1.27 0.74 1.68 1.56 

 + 0.16 + 0.52 + 0.18 + 0.86 + 0.48 

 N=23 N=22 N=19 N=22 N=36 

% Resorptions per Litterb 

4.88 11.03 5.57 12.91 13.75 

 + 1.31 + 4.90 + 1.40 + 6.21 + 4.52 

 N=23 N=22 N=19 N=22 N=36 

No. Litters with Resorptions 

 11 9 10 10 20 

% Litters with Resorptions 

 47.83 40.91 52.63 45.45 55.56 
RTI-909; Project 0209189.000 Final Report 

52

Table 6. Summary and Statistical Analysis of Ovarian Corpora Lutea, Uterine Contents, Live Fetal Sex 

and Live Fetal Body Weight (page 2 of 4) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

No. Late Fetal Deaths per 

Litterb

 

0.13 0.00 0.11 0.09 0.03 

 + 0.07 + 0.00 + 0.07 + 0.06 + 0.03 

 N=23 N=22 N=19 N=22 N=36 

%Late Fetal Deaths per 

Litterb

 

 1.02 0.00 0.70 0.65 0.20 

 + 0.56 + 0.00 + 0.49 + 0.45 + 0.20 

 N=23 N=22 N=19 N=22 N=36 

No. Litters with Late Fetal 

Deaths 

 

 3 0 2 2 1 

% Litters with Late Fetal 

Deaths 

 

 13.04 0.00 10.53 9.09 2.78 

No. Nonlive Implants per 

Litterb,d

 

0.74 1.27 0.84 1.77 1.58 

 + 0.19 + 0.52 + 0.22 + 0.86 + 0.48 

 N=23 N=22 N=19 N=22 N=36 

% Nonlive Implants per 

Litterb,d

 

5.90 11.03 6.28 13.56 13.95 

 + 1.52 + 4.90 + 1.59 + 6.16 + 4.52 

 N=23 N=22 N=19 N=22 N=36 

No. Litters with Nonlive 

Implantsd

 

 11 9 10 12 20 

% Litters with Nonlive 

Implantsd

 

47.83 40.91 52.63 54.55 55.56 

No. Litters with 100% Nonlive 

Implantsd

 

0 1 0 2 3 

% Litters with 100% Nonlive 

Implantsd

 

0.00 4.55 0.00 9.09 8.33 
RTI-909; Project 0209189.000 Final Report 

53

Table 6. Summary and Statistical Analysis of Ovarian Corpora Lutea, Uterine Contents, Live Fetal Sex 

and Live Fetal Body Weight (page 3 of 4) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

No. Adversely Affected 

Implants per Litterb,e

 

0.83 1.36 0.89 1.82 1.78 

 + 0.20 + 0.52 + 0.23 + 0.85 + 0.48 

 N=23 N=22 N=19 N=22 N=36 

% Adversely Affected 

Implants per Litterb,e

 

 6.69 11.66 6.63 13.87 15.38 

 + 1.64 + 4.85 + 1.63 + 6.15 + 4.50 

 N=23 N=22 N=19 N=22 N=36 

No. Litters with Adversely 

Affected Implantse

 

 12 11 10 12 21 

% Litters with Adversely 

Affected Implantse

 

52.17 50.00 52.63 54.55 58.33 

LIVE LITTERSf

: 23 21 19 20 33 

No. Live Fetuses per Litterb 

12.00 11.24 11.84 12.60 12.33 

 + 0.39 + 0.68 + 0.27 + 0.49 + 0.26 

 N=23 N=21 N=19 N=20 N=33 

% Male Fetuses per Litterb 

 50.03 46.46 52.95 44.67 45.58 

 + 3.11 + 3.82 + 3.70 + 3.14 + 2.99 

 N=23 N=21 N=19 N=20 N=33 

No. Male Fetuses per 

Litterb

 

 6.09 5.38 6.21 5.65 5.61 

 + 0.47 + 0.45 + 0.41 + 0.48 + 0.36 

 N=23 N=21 N=19 N=20 N=33 
RTI-909; Project 0209189.000 Final Report 

54

Table 6. Summary and Statistical Analysis of Ovarian Corpora Lutea, Uterine Contents, Live Fetal Sex 

and Live Fetal Body Weight (page 4 of 4) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

No. Female Fetuses 

per Litterb

 

5.91 5.86 5.63 6.95 6.73 

 + 0.37 + 0.52 + 0.48 + 0.47 + 0.39 

 N=23 N=21 N=19 N=20 N=33 

Average Fetal Body 

Weight (g) per Litterb

 

 0.9994 1.0114 0.9471 0.9492 1.0248 

 +0.0265 +0.0212 +0.0241 +0.0288 +0.0249 

 N=23 N=21 N=19 N=20 N=33 

Average Male Fetal Body Weight 

(g) per Litterb

 

 1.0114 1.0088 0.9605 0.9722 1.0367 

 +0.0309 +0.0166 +0.0254 +0.0311 +0.0261 

 N=23 N=20g N=19 N=20 N=33 

Average Female Fetal Body Weight 

(g) per Litterb

 

0.9961 0.9937 0.9344 0.9343 1.0141 

 +0.0246 +0.0227 +0.0231 +0.0281 +0.0239 

 N=23 N=21 N=19 N=20 N=33 

aIncludes all dams pregnant at terminal sacrifice on gestational day 17; litter size = no. implantation sites 

per dam. 

bReported as the mean + S.E.M. 

cDecrease in N is due to the right ovary for one female inadvertently being lost prior to the corpora lutea 

being counted. 

dNonlive = late fetal deaths plus resorptions. 

eAdversely affected = nonlive plus malformed. 

f

Includes only dams with live fetuses; litter size = no. live fetuses per dam. 

gDecrease in N is due to one litter having female fetuses only. 
RTI-909; Project 0209189.000 Final Report 

55

Table 7. Summary and Statistical Analysis of Fetal External Malformations and Variations (page 1 of 3) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

No. Fetuses Examineda 

276 236 225 252 407 

No. Litters Examinedb 

23 21 19 20 33 

No. Fetuses with External Malformations 

per Litterc,d

 

0.09 0.10 0.05 0.05 0.21 

 + 0.06 + 0.07 + 0.05 + 0.05 + 0.11 

N=23 N=21 N=19 N=20 N=33 

No. Male Fetuses with External 

Malformations per Litterc,d

 

0.04 0.05 0.05 0.00 0.09 

 + 0.04 + 0.05 + 0.05 + 0.00 + 0.05 

N=23 N=20 N=19 N=20 N=33 

No. Female Fetuses with External 

Malformations per Litterc,d

 

0.04 0.05 0.00 0.05 0.12 

 + 0.04 + 0.05 + 0.00 + 0.05 + 0.07 

N=23 N=21 N=19 N=20 N=33 

% Fetuses with External Malformations per 

Litterc,d

 

0.85 0.66 0.38 0.36 1.64 

 + 0.61 + 0.46 + 0.38 + 0.36 + 0.85 

N=23 N=21 N=19 N=20 N=33 

% Male Fetuses with External 

Malformations per Litterc,d

 

0.62 0.83 0.88 0.00 1.89 

 + 0.62 + 0.83 + 0.88 + 0.00 + 1.16 

N=23 N=20 N=19 N=20 N=33 

% Female Fetuses with External Malformations per 

Litterc,d

 

0.72 0.95 0.00 1.25 1.29 

 + 0.72 + 0.95 + 0.00 + 1.25 + 0.74 

N=23 N=21 N=19 N=20 N=33 
RTI-909; Project 0209189.000 Final Report 

56

Table 7. Summary and Statistical Analysis of Fetal External Malformations and Variations (page 2 of 3) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

No. Fetuses with External 

Malformationsd

 

2 2 1 1 7 

% Fetuses with External 

Malformationsd

 

0.72 0.85 0.44 0.40 1.72 

No. Litters with External 

Malformationse

 

2 2 1 1 4 

% Litters with External 

Malformationse

 

8.70 9.52 5.26 5.00 12.12 

No. Fetuses with External 

Variations per Litterc,d

 

0.13 0.14 0.11 0.15 0.00 

 + 0.07 + 0.10 + 0.07 + 0.08 + 0.00 

 N=23 N=21 N=19 N=20 N=33 

No. Male Fetuses with External 

Variations per Litterc,d

 

0.09 0.05 0.05 0.05 0.00 

 + 0.06 + 0.05 + 0.05 + 0.05 + 0.00 

 N=23 N=20 N=19 N=20 N=33 

No. Female Fetuses with External 

Variations per Litterc,d

 

0.04 0.10 0.05 0.10 0.00 

 + 0.04 + 0.10 + 0.05 + 0.07 + 0.00 

 N=23 N=21 N=19 N=20 N=33 

% Fetuses with External Variations per 

Litterc,d

 

1.34 1.27 0.81 1.26 0.00 

 + 0.76 + 0.99 + 0.56 + 0.69 + 0.00 

 N=23 N=21 N=19 N=20 N=33 

% Male Fetuses with External 

Variations per Litterc,d

 

1.45 0.56 0.66 1.00 0.00 

 + 1.00 + 0.56 + 0.66 + 1.00 + 0.00 

 N=23 N=20 N=19 N=20 N=33 
RTI-909; Project 0209189.000 Final Report 

57

Table 7. Summary and Statistical Analysis of Fetal External Malformations and Variations (page 3 of 3) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

% Female Fetuses with External 

Variations per Litterc,d

 

0.72 1.59 1.05 1.39 0.00 

 + 0.72 + 1.59 + 1.05 + 0.98 + 0.00 

 N=23 N=21 N=19 N=20 N=33 

No. Fetuses with External 

Variationsd

 

3 3 2 3 0 

% Fetuses with External 

Variationsd

 

1.09 1.27 0.89 1.19 0.00 

No. Litters with External 

Variationse

 

3 2 2 3 0 

% Litters with External 

Variationse

 

13.04 9.52 10.53 15.00 0.00 

aOnly live fetuses were examined for malformations and variations. 

bIncludes only litters with live fetuses. 

cReported as the mean + S.E.M. 

dFetuses with one or more malformations or variations. 

eLitters with one or more fetuses with malformations or variations. 
RTI-909; Project 0209189.000 Final Report 

58

Table 8. Summary of Morphological Abnormalities in CD-1 Mouse Fetuses: Listing by Defect Typea 

(page 1 of 1) 

Gasoline MTBE Vapor Condensate (mg/m3, inhaled) 

Dosed gd 5-16 Dosed gd 5-10 

 0 2000 10,000 20,000 30,000 

EXTERNAL MALFORMATIONS 

Total No. of Fetuses Examined for 

External Malformationsb

276 236 225 252 407 

No. of Fetuses with External 

Malformationsc

2 2 1 1 7 

% Fetuses with External 

Malformations 

0.7% 0.8% 0.4% 0.4% 1.7% 

Total No. of Litters Examined for 

External Malformationsd

23 21 19 20 33 

No. of Litters with External 

Malformationse

2 2 1 1 4 

% Litters with External 

Malformations 

8.7% 9.5% 5.3% 5.0% 12.1% 

Encephalocele 1(1) 

Cleft Palate 2(2) 1(1) 1(1) 1(1) 7(4) 

Gastroschisis 1(1) 

EXTERNAL VARIATIONS 

Total No. of Fetuses Examined for 

External Variationsb

276 236 225 252 407 

No. of Fetuses with External 

Variationsc

3 3 2 3 0 

% Fetuses with External Variations 1.1% 1.3% 0.9% 1.2% 0.0% 

Total No. of Litters Examined for 

External Variationsd

23 21 19 20 33 

No. of Litters with External 

Variationse

3 2 2 3 0 

% Litters with External Variations 13.0% 9.5% 10.5% 15.0% 0.0% 

Abnormal Rugae in Midline of Palate 1(1) 1(1) 

Hematoma: Face 2(1) 

Hematoma: Head 2(2) 1(1) 

Hematoma: Neck 1(1) 1(1) 1(1) 2(2) 

Hematoma: Shoulder 1(1) 

aA single fetus may be represented more than once in listing individual defects. Data are presented as 

the number of fetuses (number of litters). 

bOnly live fetuses were included. 

cFetuses with one or more malformations/variations. 

dIncludes only litters with live fetuses. 

eLitters with one or more malformed/variant fetuses. 
RTI-909; Project 0209189.000 Final Report 

59

Table 9. External Malformations in Control CD-1® Mouse Litters From Studies Performed for 

Governmental Clients at RTI From 1997 to 2002 (page 1 of 1) 

Control Group With Gastroschisisb

Study 

Code Year Study Typea No. 

Dams 

No. 

Fetuses 

No. 

Fetuses 

No. 

Litters 

Incidence of External 

Malformations 

No. Fetuses (No. Litters) 

A 2002 RF 10 138 0 0 1 (1) cleft palate 

B 2002 RF 9 123 0 0 1 (1) exencephaly 

C 1999 RF 15 184 0 0 0 

D 1999 RF 15 200 0 0 0 

E 2000 RF 14 172 0 0 0 

F 1999 RF 15 187 0 0 0 

G 2000 RF 12 165 0 0 0 

H 1999 D 24 302 0 0 0 

I 2000 D 24 326 0 0 2 (1) cleft palate 

J 1999 D 23 291 0 0 0 

K 1997 D 22 271 0 0 1 (1) cleft palate 

L 2000 D 23 283 0 0 1 (1) exencephaly 

M 2001 D 24 270 0 0 1 (1) cleft palate 

N 2002 D 20 254 0 0 6 (4) cleft palate 

O 2002 D 22 279 0 0 7 (3) cleft palate 

P 2000 D 16 196 0 0 0 

TOTAL 288 3641 0 0 18 (11) cleft palate 

2 (2) exencephaly 

a

 RF = range-finding study D = definitive study 

b

 There were also no fetuses with ectopia cordis 
Appendix I: 

Inhalation Report 














































STUDY FILE NOTE 

Study Number: 04-4262/4263 Effective Date: 9DecO8 

cc: 

Subject: Ml RAN LOQ 

The control chamber limit of quantification was estimated at 433 mg/m3 based on the 

extrapolated value for an absorbance reading of 0.01 which Is considered the lowest practical 

reading above the baseline. Since the nominal to measured ratio for even the low exposure level 

for the main study was close to 1:1, we did not see need to change the calibration curve. 

Prepared by and 

Principal Investigator 

Approval: • Date: 
Appendix II: 

Individual Animal Data Tables 
Table of Contents 

A-1 Individual Maternal Body Weights and Organ Weights (g) ................................. 1 

A-2 Individual Maternal Clinical Observations........................................................... 5 

A-3 Individual Maternal Feed Consumption (g/day) .................................................. 6 

A-4 Individual Embryo/Fetal Data.............................................................................. 11 
Appendix II 1 Table A-1. Individual Maternal Body Weights and Organ Weights (g) (page 1 of 4) Gestational Day Dosea Dam ID 0 5 6 7 8 9 10 11 12 13 14 15 16 17 17b Gravid Uterine Wt. Liver Wt. Paired Adrenal Gland Wt. Paired Kidney Wt. 0 1801 23.7 25.3 25.6 26.9 27.8 29.5 29.4 31.0 33.4 35.7 37.4 40.2 42.7 45.7 44.04 14.4811 2.3692 0.0136 0.4460 1802 27.4 28.6 29.3 30.1 30.7 31.0 32.3 34.7 37.2 40.0 41.5 44.1 49.0 52.3 51.46 19.7607 2.6311 0.0158 0.4819 1803 27.5 27.3 28.6 28.6 29.3 29.6 29.9 31.9 33.1 34.5 36.4 39.0 41.8 44.2 41.65 13.6798 2.1015 0.0115 0.3775 1804 24.0 24.5 24.9 25.6 26.2 26.3 27.4 29.6 31.8 34.3 36.3 40.2 43.3 46.1 45.15 17.7023 2.3577 0.0165 0.4112 1805 27.2 27.3 27.6 28.8 30.0 29.9 30.7 32.9 34.9 36.3 38.2 41.8 44.4 47.7 46.02 16.6375 2.2176 0.0115 0.3908 1806 27.2 27.5 28.3 29.2 29.5 30.0 31.0 32.9 35.6 37.4 39.6 43.5 46.2 49.3 48.23 18.2375 2.4033 0.0164 0.4395 1807 23.9 26.2 25.7 26.9 27.3 27.9 29.9 31.7 33.1 35.9 37.2 39.9 43.8 48.4 47.32 18.3623 2.4555 .c 0.4020 1808 26.4 26.7 26.9 27.6 27.7 27.6 28.7 30.3 32.8 35.1 38.3 40.1 43.6 47.8 46.10 17.9075 2.3041 0.0141 0.4291 1809 26.5 28.4 29.2 29.0 29.6 30.2 31.1 32.4 34.6 36.2 38.0 39.4 41.1 44.4 43.49 14.7802 2.2250 0.0127 0.3379 1810 27.8 28.4 29.6 30.3 29.7 30.5 31.6 33.7 34.3 36.0 39.0 41.1 43.4 46.2 44.21 13.6742 2.3782 0.0128 0.3950 1811 27.9 27.6 28.4 28.6 29.5 29.8 31.3 34.0 37.3 40.1 41.2 43.7 48.6 53.1 52.05 20.7503 2.9608 0.0135 0.5055 1812 25.0 25.0 25.5 25.9 26.7 26.5 28.1 29.3 31.5 33.5 36.2 39.2 42.4 45.3 44.26 17.3355 2.2345 0.0135 0.4018 1813 27.2 28.3 29.2 30.2 30.7 30.9 32.5 33.5 35.0 36.8 39.1 42.3 44.8 48.3 46.90 15.3242 2.6188 0.0211 0.4432 1814 27.2 27.7 28.5 29.3 30.1 30.6 32.2 33.3 35.8 37.9 40.9 43.6 46.8 50.3 48.78 17.9133 2.7351 0.0106 0.4211 1815 28.3 28.6 29.3 30.3 30.9 31.2 32.9 35.3 36.6 38.4 40.6 42.8 45.9 49.2 47.46 16.4148 2.7521 0.0135 0.4091 1816 28.7 30.0 31.9 32.3 32.5 33.1 34.4 36.8 38.9 40.5 43.5 46.3 48.2 52.4 51.34 19.6942 2.6059 0.0132 0.4968 1817 23.9 24.6 24.5 24.6 25.1 25.4 26.3 27.8 29.6 31.5 33.6 36.0 38.9 40.5 40.07 13.4026 2.0213 0.0130 0.3758 1818 28.5 29.9 31.0 30.5 31.1 32.2 33.9 36.8 38.7 40.8 43.2 46.8 49.9 52.5 51.75 20.6578 2.5824 0.0112 0.4805 1819 28.8 30.0 31.2 30.9 31.2 32.5 34.0 36.1 38.1 40.4 43.0 46.1 49.4 51.8 51.28 20.1298 2.5947 0.0192 0.4735 1820 25.2 26.8 27.5 28.1 28.8 29.7 30.5 33.2 35.0 36.6 40.0 43.0 46.2 49.7 48.71 18.7321 2.3504 0.0088 0.4119 1821 24.3 25.4 25.7 26.5 26.6 27.2 28.0 29.3 31.6 33.6 35.5 38.0 41.5 43.9 43.40 15.6224 2.1432 0.0149 0.4096 1822 28.9 30.7 30.9 31.5 31.5 32.1 33.1 34.3 36.9 39.2 41.1 44.5 48.9 52.4 51.15 18.5153 2.6422 0.0099 0.4761 1823 28.8 29.0 28.9 29.3 29.6 29.7 31.5 34.0 36.3 38.7 41.6 44.9 48.9 51.8 49.47 17.9535 2.6913 0.0119 0.4204 2000 2801 25.0 27.6 27.9 28.4 28.5 28.9 28.9 29.7 30.2 30.1 30.5 32.0 32.4 33.5 31.58 2.3762 1.8423 0.0139 0.4669 2802 27.0 29.1 29.9 31.1 31.7 32.3 33.2 34.5 35.8 36.9 38.6 41.0 44.6 46.7 45.48 13.0643 2.4958 0.0162 0.4533 2803 27.5 27.1 27.3 28.6 28.2 28.5 30.1 34.4 36.3 37.8 40.6 45.8 49.6 52.9 50.08 21.7074 2.1868 0.0110 0.3865 2804 24.3 25.3 25.4 26.5 27.0 26.8 27.9 29.7 32.3 33.9 36.5 39.5 42.6 44.8 43.98 15.4744 2.4670 0.0114 0.4041 2805 26.7 26.0 26.2 27.0 28.4 28.3 29.1 30.7 33.1 34.8 36.8 40.2 43.7 45.5 44.36 16.1582 2.2875 0.0159 0.3687 2806 27.4 27.6 28.8 29.1 29.6 30.2 31.4 34.1 36.1 37.5 40.3 43.9 46.2 50.2 49.83 17.2433 2.7615 0.0162 0.4452 2807 24.6 24.8 26.4 27.7 27.5 28.0 29.3 31.2 32.9 34.8 36.0 38.4 41.6 44.6 43.51 14.5031 2.6123 0.0154 0.4026 2808 26.4 28.8 30.3 30.7 30.7 31.2 32.5 34.4 35.9 37.7 39.3 40.8 42.5 45.0 44.13 12.2719 2.5176 0.0146 0.4944 2809 26.8 30.4 31.0 31.5 32.6 32.9 34.7 36.5 38.8 40.0 40.9 44.1 47.6 49.5 48.54 15.9050 2.9708 0.0161 0.4968 2810 27.7 30.5 30.1 30.3 31.7 32.0 32.6 35.1 36.4 37.6 38.9 42.0 45.1 48.1 46.70 14.7170 2.5925 0.0142 0.4062 2811 28.0 28.6 29.0 29.6 30.0 30.7 31.8 33.7 35.4 37.6 39.8 42.1 45.3 47.8 46.65 17.7486 2.3583 0.0141 0.3872 2812 29.8 30.7 31.9 32.0 32.3 33.6 34.8 37.4 40.7 42.5 45.5 48.7 52.7 56.9 55.09 20.6185 2.9510 0.0177 0.4590 2813 25.2 25.3 26.0 26.0 26.7 26.6 26.3 26.1 25.9 24.9 24.4 25.1 24.7 26.5 24.98 0.2012 1.4584 0.0094 0.4166 2814 27.0 26.7 27.6 28.0 28.5 29.0 30.2 32.7 34.6 36.6 37.7 40.1 43.3 46.5 45.18 14.7611 2.5448 0.0227 0.4334 
Appendix II 2 Table A-1. Individual Maternal Body Weights and Organ Weights (g) (page 2 of 4) Gestational Day Dosea Dam ID 0 5 6 7 8 9 10 11 12 13 14 15 16 17 17b Gravid Uterine Wt. Liver Wt. Paired Adrenal Gland Wt. Paired Kidney Wt. 20000 2815 27.5 31.4 32.4 32.7 33.4 33.9 36.0 38.0 40.3 41.5 44.1 47.4 51.5 54.2 53.35 18.9077 3.1841 0.0163 0.4782 2816 28.3 27.8 29.1 30.4 30.6 30.5 32.1 34.6 37.8 39.0 41.8 43.9 48.0 51.4 49.86 18.2901 2.6670 0.0133 0.4295 2817 28.8 29.8 29.7 30.0 30.6 31.0 32.2 34.0 35.4 36.7 38.7 41.1 43.8 46.8 46.53 17.2023 2.2908 0.0141 0.4120 2818 25.6 27.7 29.1 30.1 30.1 30.9 32.9 34.9 37.6 39.7 42.4 45.6 49.4 52.8 52.35 21.5024 2.8345 0.0151 0.5062 2819 28.2 30.7 31.5 31.9 32.5 33.3 34.7 37.2 39.5 42.0 44.1 47.2 50.7 55.0 53.58 18.9426 3.0684 0.0129 0.5620 2820 29.1 30.3 31.4 31.6 32.7 33.3 35.3 38.4 39.9 41.2 44.5 47.5 50.9 54.7 53.60 18.8395 2.9602 0.0172 0.5350 2821 .d 2822 27.3 27.0 27.7 28.6 28.7 28.8 30.1 31.9 33.9 35.1 38.5 41.2 44.7 47.7 46.32 15.2662 2.5073 0.0069 0.4186 2823 29.3 30.8 31.5 32.4 32.7 33.3 34.3 36.1 38.3 39.9 42.3 46.2 50.4 54.0 51.95 16.8460 3.1252 0.0127 0.4374 10000 3801 25.4 26.5 26.8 27.3 27.5 28.4 29.6 31.8 33.7 35.5 37.1 39.8 42.3 44.4 44.62 14.7301 2.7557 0.0115 0.4576 3802 .d 3803 27.5 28.0 28.7 29.2 30.3 30.4 31.3 33.4 35.5 37.2 39.3 41.7 44.1 47.1 47.34 16.9253 2.4204 0.0121 0.4191 3804 25.4 27.5 28.4 29.0 30.2 30.7 33.5 35.1 36.7 38.3 40.7 43.8 46.9 49.7 48.87 16.1002 2.6020 0.0127 0.4318 3805 26.5 28.2 28.7 29.0 30.1 31.1 32.5 35.6 37.3 38.9 41.5 44.7 46.9 49.3 48.51 17.6251 2.5656 0.0140 0.4162 3806 27.6 29.4 30.1 31.0 32.0 33.0 34.9 37.6 39.7 42.2 45.0 48.0 51.9 55.2 53.77 19.7811 2.9632 0.0135 0.4945 3807 25.0 24.8 25.3 25.7 26.7 27.3 28.4 30.5 32.1 33.7 35.2 37.4 41.0 44.3 43.27 14.5264 2.8788 0.0106 0.4709 3808 26.2 26.3 26.3 27.0 27.3 27.3 28.1 30.1 32.7 34.3 35.8 38.1 40.0 42.5 41.96 13.4726 2.4245 0.0157 0.4236 3809 26.9 27.4 27.6 28.5 28.8 29.2 30.4 32.1 34.0 35.1 37.0 39.6 42.7 45.2 44.35 16.7280 2.4484 0.0138 0.4345 3810 27.5 28.9 29.8 30.1 30.5 30.9 31.5 34.2 36.0 38.3 41.1 42.6 45.7 48.9 47.29 16.8350 2.5713 0.0152 0.4403 3811 28.1 26.1 27.2 27.2 27.9 27.7 28.8 30.3 32.2 34.4 36.5 39.3 41.7 44.3 43.58 14.9477 2.5122 0.0122 0.4060 3812 29.1 29.1 29.5 30.3 30.7 31.1 32.4 34.3 36.3 38.1 40.7 43.9 47.2 50.3 48.94 18.1387 2.7584 0.0129 0.4366 3813 25.5 24.2 27.3 27.1 27.1 27.6 29.3 30.5 32.0 34.4 35.7 39.4 41.8 44.8 43.89 15.3821 2.6385 0.0116 0.4457 3814 .e 3815 27.7 29.0 30.5 31.2 31.8 32.7 35.1 37.0 38.4 40.5 42.1 45.7 48.9 52.8 52.65 17.5735 2.904f 0.0141 0.4550 3816 28.2 28.0 29.0 29.6 30.2 30.3 32.0 34.5 36.3 38.7 41.3 43.9 48.0 51.5 50.10 18.6991 2.9257 0.0135 0.4536 3817 .d 3818 25.8 27.3 28.8 28.7 28.5 30.5 30.3 32.4 34.1 35.4 37.2 40.5 43.4 46.1 45.33 14.8345 2.5348 0.0141 0.4111 3819 28.2 28.8 29.4 29.6 29.9 30.4 32.0 32.9 35.3 37.2 38.6 41.1 44.2 47.6 46.66 16.0488 2.9220 0.0151 0.4295 3820 26.9 30.3 32.1 32.4 33.6 34.7 35.4 37.9 39.0 41.0 43.2 45.6 48.7 53.2 52.04 16.8824 3.1119 0.0104 0.4274 3821 27.3 29.7 30.1 30.8 30.6 31.4 33.5 34.6 37.2 38.3 41.2 45.0 48.1 51.3 50.73 18.0837 3.2004 0.0141 0.4744 3822 28.1 29.1 29.4 29.9 30.8 31.3 31.4 33.7 35.1 37.7 39.8 42.5 46.7 50.1 48.90 17.5758 2.6313 .c 0.4213 3823 .d 20000 4801 25.7 26.3 26.7 27.7 28.0 28.1 28.6 30.4 32.5 33.8 36.7 39.0 42.6 45.0 44.82 16.7765 2.6705 0.0084 0.4149 4802 26.4 29.1 29.1 30.3 30.3 31.3 32.0 34.0 36.8 38.8 40.6 43.6 46.3 48.6 48.83 17.0931 2.8105 0.0141 0.5266 4803 28.0 30.0 30.4 31.3 31.4 31.4 32.2 34.7 36.9 38.6 41.4 43.9 47.3 50.8 50.04 18.8684 2.4162 0.0127 0.4472 
Appendix II 3 Table A-1. Individual Maternal Body Weights and Organ Weights (g) (page 3 of 4) Gestational Day Dosea Dam ID 0 5 6 7 8 9 10 11 12 13 14 15 16 17 17b Gravid Uterine Wt. Liver Wt. Paired Adrenal Gland Wt. Paired Kidney Wt. 20000 4804 29.7 29.8 30.5 31.0 31.3 31.7 32.6 34.6 37.6 39.0 41.3 43.5 47.0 49.3 49.19 17.6044 2.6289 0.0172 0.4266 4805 25.7 26.8 27.6 28.3 28.7 28.7 29.3 30.9 33.5 35.4 37.1 40.3 42.7 46.6 45.87 16.9954 2.6732 0.0150 0.4320 4806 26.4 28.8 29.2 29.8 30.9 31.0 32.4 33.5 35.6 38.2 39.2 42.5 44.9 47.4 47.48 17.0330 2.8556 0.0132 0.4188 4807 27.7 29.0 28.9 30.1 30.8 30.7 31.6 34.3 36.2 38.3 41.0 44.2 46.9 50.4 49.18 17.5032 2.8624 0.0165 0.4116 4808 25.1 26.7 27.6 28.3 28.5 28.9 30.2 32.1 34.3 36.2 38.8 41.8 45.9 49.4 48.53 18.8523 2.8895 0.0168 0.4153 4809 26.0 29.3 29.6 30.8 31.6 32.3 34.0 36.7 39.6 41.8 44.9 47.5 52.5 54.8 55.12 22.6107 2.9528 0.0137 0.4431 4810 27.0 26.6 27.5 28.2 28.3 28.8 30.0 31.6 33.5 34.2 37.0 39.7 43.2 46.2 45.12 16.4734 2.7402 0.0161 0.3932 4811 27.5 28.2 29.9 30.9 31.3 32.5 34.3 36.0 38.2 39.1 42.4 43.6 46.4 51.0 49.15 19.6011 2.8417 0.0131 0.3939 4812 28.2 27.7 28.2 28.2 28.5 29.1 29.8 30.9 33.2 34.3 36.5 38.7 41.0 43.5 42.80 15.8511 2.2713 0.0131 0.3702 4813 29.0 29.1 29.5 30.5 30.4 31.8 32.9 36.5 39.2 41.1 44.2 47.4 51.8 55.3 53.28 21.9836 2.9297 0.0106 0.4795 4814 25.6 27.3 27.7 27.8 28.1 28.4 29.7 31.1 32.1 33.6 34.7 37.5 38.2 40.0 38.65 10.0827 2.2418 0.0152 0.4031 4815 .d 4816 27.7 29.2 30.3 30.2 31.2 31.3 32.0 34.0 35.3 37.4 39.6 43.2 45.7 49.0 47.99 17.4621 2.6378 0.0105 0.4726 4817 28.2 28.0 29.0 29.5 30.3 30.9 32.0 33.6 35.7 37.5 39.6 42.5 45.9 49.2 48.70 17.1257 2.8046 0.0149 0.4653 4818 30.1 30.6 30.9 31.3 31.3 32.3 31.9 32.0 31.3 31.9 30.6 30.5 30.9 31.4 29.96 0.1257 1.8489 0.0149 0.4931 4819 26.0 26.5 26.2 26.3 27.2 27.4 27.3 27.6 27.7 27.0 27.7 27.3 27.3 27.0 26.27 0.1142 1.7097 0.0124 0.4325 4820 27.9 28.6 29.1 29.0 29.4 30.5 31.7 33.2 35.7 36.7 39.3 41.6 44.4 47.7 46.95 15.0383 2.7616 0.0165 0.4797 4821 27.3 29.3 29.8 30.3 31.2 31.8 32.4 34.6 36.6 38.9 40.8 44.3 47.7 50.5 50.09 18.7231 2.8499 0.0104 0.3662 4822 27.4 28.7 29.2 29.7 30.1 30.1 31.0 31.5 34.1 35.9 37.4 40.8 44.4 47.4 45.92 15.4136 2.7219 0.0139 0.4855 4823 28.1 31.5 31.4 32.2 32.1 33.5 34.0 35.6 37.3 39.3 40.7 43.3 44.7 46.7 46.09 14.5411 2.7599 0.0112 0.4560 30000 5801 .d 5802 26.2 27.5 26.8 28.1 28.6 29.5 30.4 32.0 35.1 37.6 40.6 43.6 47.1 50.0 49.36 18.8132 2.2720 0.0147 0.4919 5803 26.3 27.4 28.0 28.5 29.5 30.0 30.3 33.3 35.3 37.1 39.9 43.5 45.3 48.6 46.62 18.7458 1.9859 0.0092 0.3940 5804 28.2 29.5 29.5 30.3 31.2 32.0 32.7 34.5 36.5 39.6 42.3 45.8 48.7 50.6 51.20 18.2262 2.4269 0.0115 0.5063 5805 28.2 28.4 29.3 29.5 30.3 30.9 30.9 32.7 34.5 36.8 39.1 36.0 42.6 46.5 45.64 18.1812 2.0216 0.0131 0.4078 5806 29.6 30.7 31.0 32.7 33.0 34.2 34.8 36.7 38.5 40.9 44.7 48.6 51.8 55.1 54.57 22.0056 2.3285 0.0131 0.4011 5807 25.9 26.4 27.1 27.8 29.0 29.6 30.0 31.9 34.7 36.8 40.3 42.8 45.4 48.6 47.78 18.3769 2.3540 0.0126 0.3456 5808 25.9 26.6 26.7 27.9 29.0 28.9 29.7 32.1 34.1 36.7 39.5 42.0 45.3 47.7 47.72 17.6901 2.3910 0.0138 0.4082 5809 26.3 26.6 27.2 28.3 29.1 29.3 30.8 32.7 35.4 37.1 40.8 43.6 46.0 49.8 48.81 18.6972 2.2420 0.0139 0.4398 5810 29.2 29.9 29.9 30.1 31.1 30.7 31.8 33.8 36.7 38.7 41.9 44.6 48.4 51.0 49.73 19.1084 2.5462 0.0119 0.4036 5811 31.3 31.9 32.1 32.6 33.6 33.8 35.1 37.3 40.3 43.0 47.0 50.6 53.8 57.0 55.58 21.4731 2.8532 0.0148 0.4761 5812 25.6 27.5 27.3 28.0 28.4 29.4 30.3 31.7 34.2 36.9 38.9 42.0 44.8 47.6 46.86 16.2375 2.5839 0.0155 0.5004 5813 25.7 26.7 27.0 27.8 27.3 26.5 26.2 26.5 27.1 27.6 27.3 26.7 25.9 27.3 26.21 0.1443 1.7424 0.0151 0.4138 5814 25.8 28.4 28.4 29.1 29.6 30.1 31.1 32.7 35.7 38.4 40.8 43.5 47.4 50.9 50.04 17.4432 2.8111 0.0134 0.4814 5815 25.9 26.4 27.3 28.5 28.5 28.8 29.7 31.8 34.2 36.5 38.2 41.2 44.9 47.7 46.86 17.2691 2.5748 0.0122 0.3722 5816 27.1 28.3 29.4 31.0 31.2 32.3 34.1 35.6 38.4 40.9 43.4 46.8 49.3 51.7 51.43 20.6765 2.6542 0.0140 0.4346 5817 .d
Appendix II 4 Table A-1. Individual Maternal Body Weights and Organ Weights (g) (page 4 of 4) Gestational Day Dosea Dam ID 0 5 6 7 8 9 10 11 12 13 14 15 16 17 17b Gravid Uterine Wt. Liver Wt. Paired Adrenal Gland Wt. Paired Kidney Wt. 30000 5818 27.3 27.0 28.1 27.6 27.7 28.7 30.5 32.0 34.6 37.5 39.7 41.4 44.7 48.9 47.49 19.4554 2.1213 0.0136 0.4744 5819 27.4 29.0 29.6 29.6 30.1 31.2 32.5 34.3 36.4 39.2 42.1 44.9 48.2 51.8 49.80 18.6413 2.5928 0.0122 0.4614 5820 28.3 28.6 28.8 29.5 29.8 29.9 31.3 32.3 35.3 37.1 39.3 42.6 45.4 48.9 47.34 16.7165 2.3715 0.0106 0.4088 5821 28.3 29.5 30.5 32.0 32.1 33.3 34.2 35.8 38.2 40.5 41.6 44.5 48.7 51.5 50.76 17.7549 2.8188 0.0123 0.4731 5822 28.4 28.4 28.3 29.0 28.2 28.5 29.3 30.5 32.8 34.2 36.8 39.3 41.4 44.9 43.85 16.2522 2.0635 0.0116 0.3750 5823 28.7 29.1 30.0 30.7 31.6 33.1 34.1 36.2 39.2 41.3 44.6 49.0 51.5 55.1 55.01 22.3565 2.3108 0.0144 0.3464 5824 25.8 24.9 25.5 24.2 23.4 24.0 23.8 24.0 25.2 25.4 25.5 25.2 25.0 25.7 25.39 0.1097 1.4946 0.0172 0.3639 5825 26.2 26.8 28.5 28.6 29.0 29.8 30.1 31.8 34.4 35.3 36.9 40.3 43.0 46.1 45.25 14.9805 2.3879 0.0143 0.4199 5826 26.6 27.1 28.3 28.5 28.7 29.2 30.3 32.3 35.8 38.1 41.0 44.1 47.2 50.7 50.20 19.2251 2.7888 0.0131 0.4647 5827 27.7 26.4 27.2 27.1 27.8 28.1 29.0 31.1 33.7 35.4 37.0 39.9 42.9 46.6 45.81 15.3833 2.3213 0.0143 0.3784 5828 27.8 28.5 29.3 28.9 29.1 29.9 30.9 32.9 36.5 37.6 39.1 42.7 44.2 47.7 46.68 15.6981 2.2852 0.0151 0.4336 5829 28.1 28.7 29.1 29.0 29.5 30.1 31.1 33.0 35.4 36.2 38.2 41.1 44.1 47.0 45.62 14.9195 2.4199 0.0111 0.4803 5830 30.3 33.4 33.1 33.0 33.5 34.3 35.0 37.2 40.1 42.8 45.4 50.5 53.5 58.0 56.48 20.2425 3.0487 0.0150 0.4365 5831 26.3 28.0 28.2 28.7 29.0 29.5 30.1 33.4 35.4 37.1 39.8 42.9 46.4 49.5 48.76 18.3770 2.6777 0.0132 0.4656 5832 26.9 30.0 30.2 31.4 32.2 33.2 35.0 37.4 39.3 41.4 44.0 47.3 51.1 54.7 54.13 20.3232 3.2612 0.0151 0.4721 5833 27.0 27.5 27.6 28.4 28.7 29.2 30.4 32.1 34.5 36.0 38.5 41.3 44.6 47.8 47.02 16.3016 2.7776 0.0161 0.4644 5834 27.9 27.3 28.0 28.2 29.5 29.1 31.2 32.5 33.6 36.2 38.0 39.7 42.6 45.9 44.84 14.7283 2.3049 0.0131 0.4299 5835 27.7 30.2 30.4 31.3 31.9 33.4 35.7 37.9 39.7 42.8 45.4 49.3 51.9 56.8 56.05 22.1501 2.7876 0.0131 0.4039 5836 28.1 28.4 29.3 30.1 30.5 31.6 33.1 34.4 36.6 38.5 41.1 44.9 48.9 52.4 51.13 19.7858 2.3708 0.0158 0.4420 5837 28.3 29.1 30.0 30.0 30.2 29.9 30.1 29.7 29.9 30.3 30.2 29.7 30.1 31.2 29.40 0.1544 1.8195 0.0131 0.4512 5838 28.0 28.1 28.7 28.9 30.0 31.3 31.5 32.8 35.1 37.7 39.7 43.1 46.7 49.2 48.33 17.4607 2.5002 0.0145 0.3965 aMg/m3 of gasoline MTBE vapor condensate. bBody weight at sacrifice. cPaired adrenal gland weight was a statistical outlier and therefore it was excluded. dFemale was not pregnant. eFemale was removed due to a preexisting condition. At necropsy she was found to have an undescended testis on the right and seminal vesicles and prostate to the right of the vagina and cervix. fLiver weight was inadvertently recorded to only 3 decimal places. 
Appendix II 5 

Table A-2. Individual Maternal Clinical Observations (page 1 of 1) 

Dosea Dam ID Dayb Timec Observation 

10000 3808 12 Prior Red exudate from anogenital area 

20000 4803 6 Post Lacrimation, unilateral, moderate 

 4807 5 Post Alopecia: extremities/snout, moderate 

 6 Prior Alopecia: extremities/snout, moderate 

 Post Alopecia: extremities/snout, moderate 

 7 Prior Alopecia: extremities/snout, moderate 

 Post Alopecia: extremities/snout, moderate 

 8 Prior Alopecia: extremities/snout, moderate 

 Post Alopecia: extremities/snout, moderate 

 9 Prior Alopecia: extremities/snout, moderate 

 Post Alopecia: extremities/snout, moderate 

 10 Prior Alopecia: extremities/snout, moderate 

 Post Alopecia: extremities/snout, moderate 

 11 Prior Alopecia: extremities/snout, moderate 

 Post Alopecia: extremities/snout, moderate 

 12 Prior Alopecia: extremities/snout, moderate 

 Post Alopecia: extremities/snout, moderate 

 4814 11 Post Red exudate from anogenital area 

 4823 9 Post Labored breathing 

30000 5802 6 Post Lacrimation, unilateral, moderate 

 5805 6 Post Lacrimation, bilateral, moderate 

 5824 5 Post Lacrimation, unilateral, moderate 

 5829 2 Prior Eye: enophthalmos, unilateral, left 

 3 Prior Eye: enophthalmos, unilateral, left 

 4 Prior Eye: enophthalmos, unilateral, left 

 5 Prior Eye: enophthalmos, unilateral, left 

 Post Eye: enophthalmos, unilateral, left 

 6 Prior Eye: enophthalmos, unilateral, left 

 Post Eye: enophthalmos, unilateral, left 

 7 Prior Eye: enophthalmos, unilateral, left 

 Post Eye: enophthalmos, unilateral, left 

 8 Prior Eye: enophthalmos, unilateral, left 

 Post Eye: enophthalmos, unilateral, left 

 9 Prior Eye: enophthalmos, unilateral, left 

 Post Eye: enophthalmos, unilateral, left 

 10 Prior Eye: enophthalmos, unilateral, left 

 Post Eye: enophthalmos, unilateral, left 

 11 Prior Eye: enophthalmos, unilateral, left 

 12 Prior Eye: enophthalmos, unilateral, left 

 13 Prior Eye: enophthalmos, unilateral, left 

 14 Prior Eye: enophthalmos, unilateral, left 

 15 Prior Eye: enophthalmos, unilateral, left 

 16 Prior Eye: enophthalmos, unilateral, left 

 17 Prior Eye: enophthalmos, unilateral, left 

 5838 10 Post Labored breathing 

aMg/m3 of gasoline MTBE vapor condensate. bGestational day. 

cTime is prior to dosing (Prior) or after dosing (Post). 
Appendix II 6 Table A-3. Individual Maternal Feed Consumption (g/day)a (page 1 of 5) Gestational Days Doseb Dam ID 0-5 5-6 6-7 7-8 8-9 9-10 10-11 11-12 12-13 13-14 14-15 15-16 16-17 5-10c 5-16d 10-17c 0-17 0 1801 .e 5.6 6.4 6.8 7.4 6.8 8.8 8.6 7.3 7.8 8.0 8.0 8.8 6.6 7.4 8.2 .f 1802 5.5 6.0 6.2 6.2 6.8 6.9 7.2 7.6 7.5 7.3 7.4 8.7 8.5 6.4 7.1 7.7 6.7 1803 .e .e .e .g 10.4 8.5 6.8 6.6 6.7 8.6 7.4 7.4 9.4 .f .f 7.6 .f 1804 5.6 5.1 5.8 5.8 6.8 5.8 9.4 8.2 7.0 6.8 7.2 7.9 7.9 5.9 6.9 7.8 6.6 1805 7.3 6.2 6.4 6.5 6.5 6.5 .e 9.8 6.9 6.8 7.1 7.3 7.4 6.4 .f .f .f 1806 4.9 4.9 5.9 5.7 5.7 5.6 6.1 6.0 6.5 6.2 7.5 7.1 7.1 5.6 6.1 6.6 5.8 1807 6.0 5.8 7.9 7.3 9.8 6.3 6.7 6.7 7.0 7.4 7.1 7.0 6.8 7.4 7.2 7.0 6.8 1808 5.4 5.2 5.4 5.5 5.6 5.9 5.2 5.5 5.7 6.6 6.2 6.1 6.6 5.5 5.7 6.0 5.7 1809 5.0 5.4 5.5 6.0 5.4 6.1 5.7 6.2 6.1 6.2 6.4 6.2 6.4 5.7 5.9 6.2 5.7 1810 6.5 8.7 7.1 6.1 6.6 6.7 7.7 6.6 6.4 7.9 7.3 7.0 7.9 7.0 7.1 7.3 7.0 1811 .e .g .g 6.9 14.5 8.0 7.3 11.3 7.6 7.0 7.3 8.2 8.5 10.4 9.1 8.2 .f 1812 .e 4.1 5.1 .g .e 6.7 .e 5.6 5.8 7.5 8.2 6.6 7.1 .f .f .f .f 1813 5.3 6.6 6.1 8.8 8.3 6.0 6.3 5.8 6.8 8.4 6.9 8.2 8.0 7.2 7.1 7.2 6.6 1814 .e 8.4 .g 9.0 9.7 9.7 .e 8.3 8.2 8.1 7.9 7.9 8.1 10.6 .f .f .f 1815 .e 6.0 6.8 7.2 8.2 7.1 7.3 6.9 7.1 7.9 6.9 7.5 10.2 7.1 7.2 7.7 .f 1816 7.4 8.1 .g 9.7 10.1 8.6 .e 10.2 7.3 7.6 8.2 6.5 7.9 10.8 .f .f .f 1817 7.5 .e .e 12.2 .e 8.3 8.1 11.0 9.2 6.5 7.9 7.6 5.6 .f .f 8.0 .f 1818 7.4 7.1 5.4 6.0 5.6 5.8 6.4 10.8 9.5 7.9 7.1 8.4 7.8 6.0 7.3 8.3 7.3 1819 5.0 6.1 5.5 6.7 5.2 6.0 6.6 7.2 8.1 7.1 8.2 8.9 7.2 5.9 6.9 7.6 6.3 1820 5.2 6.0 6.3 5.8 6.5 5.7 6.3 7.4 7.1 7.1 7.1 7.6 6.9 6.1 6.6 7.1 6.2 1821 7.7 4.4 6.5 7.3 7.8 6.1 6.5 7.9 6.2 6.3 8.0 7.2 6.6 6.4 6.7 7.0 7.0 1822 5.7 5.5 5.2 5.8 5.4 6.0 6.5 5.8 6.3 7.3 7.3 6.9 7.3 5.6 6.2 6.8 6.1 1823 6.2 6.3 5.7 5.7 6.9 5.6 6.1 7.0 7.0 7.0 6.8 7.5 7.0 6.0 6.5 6.9 6.5 2000 2801 5.8 6.1 5.3 6.4 7.6 6.3 6.2 6.2 6.3 6.1 6.2 5.6 5.9 6.2 6.1 2802 6.3 6.9 9.5 8.0 6.5 8.3 7.0 6.9 7.1 7.0 6.0 7.8 8.0 7.4 7.1 2803 5.3 5.8 6.2 9.5 4.5 6.0 7.5 6.7 6.2 .e .e 7.0 7.4 .f .f 2804 .e 5.5 11.2 6.6 7.7 7.5 6.5 8.4 7.6 7.4 6.9 6.3 7.2 7.4 .f 2805 4.7 4.8 5.5 6.2 6.5 6.2 6.1 6.7 6.9 6.6 6.9 7.3 6.7 6.3 5.9 2806 .h 7.7 16.0 8.2 .h 6.8 7.5 8.0 6.1 .h 6.8 7.9 7.3 .f .f 2807 .h 8.1 .g 10.9 .g 10.6 10.6 .e 7.5 7.1 6.3 8.2 6.9 .f .f 2808 7.9 9.5 8.2 7.5 6.9 7.2 9.1 8.1 7.7 8.1 9.0 8.5 7.9 8.2 8.1 2809 7.4 5.9 5.6 6.7 5.7 7.2 8.4 7.3 6.9 6.1 8.8 6.9 7.7 6.9 7.1 2810 7.5 6.0 7.1 7.7 6.8 6.9 7.6 7.2 8.0 7.1 9.3 8.1 7.6 7.4 7.5 
Appendix II 7 Table A-3. Individual Maternal Feed Consumption (g/day)a (page 2 of 5) Gestational Days Doseb Dam ID 0-5 5-6 6-7 7-8 8-9 9-10 10-11 11-12 12-13 13-14 14-15 15-16 16-17 5-10c 5-16d 10-17c 0-17 2000 2811 5.2 5.5 6.3 5.8 6.3 6.0 6.0 6.2 6.3 6.3 7.1 9.8 6.0 6.5 6.1 2812 8.2 .e 12.8 9.8 11.4 8.0 8.1 7.8 11.4 11.2 8.8 9.0 9.3 .f .f 2813 4.3 5.2 5.7 5.5 4.3 5.2 4.6 4.8 4.3 4.4 4.4 4.9 4.3 4.8 4.6 2814 6.6 8.2 6.0 6.2 6.7 6.8 7.5 7.9 7.4 7.3 7.5 8.1 8.6 7.2 7.1 2815 9.5 9.0 .e 8.2 8.3 7.5 9.3 8.8 7.0 9.0 8.0 8.4 7.3 .f .f 2816 7.7 7.2 7.6 7.7 7.9 7.0 7.3 7.6 7.5 9.0 7.7 9.0 8.8 7.8 7.8 2817 4.7 5.3 5.2 5.9 5.5 5.5 5.4 5.9 5.7 6.8 5.5 5.9 6.3 5.7 5.4 2818 4.9 6.5 6.2 7.2 6.3 .e 8.6 6.9 7.3 7.8 7.5 7.5 7.3 .f .f 2819 5.5 7.0 6.9 7.1 7.2 6.9 10.2 7.3 8.7 8.4 8.3 8.5 8.4 7.9 7.2 2820 8.2 8.2 9.5 7.4 7.4 7.9 8.4 7.7 8.6 8.2 8.5 8.7 8.7 8.2 8.3 2821 .i 2822 .h 5.0 7.0 6.5 6.5 5.5 7.3 5.9 .h 7.9 6.6 8.3 6.8 .f .f 2823 7.8 6.7 .h .g .g 7.9 7.4 7.1 8.6 7.8 9.3 9.1 9.0 .f .f 10000 3801 5.5 5.6 5.8 4.9 6.9 5.7 6.8 6.8 7.2 7.6 7.3 6.9 8.8 6.5 6.4 3802 .i 3803 .e .e 8.4 10.8 .h 6.1 6.7 .e 12.0 8.0 7.9 7.3 8.1 .f .f 3804 .e 5.9 9.4 6.8 6.6 8.1 7.4 7.3 8.3 10.3 8.2 8.2 8.4 7.9 .f 3805 .e .e 10.0 8.1 7.7 7.3 8.9 8.1 7.7 7.7 7.8 8.0 7.0 .f .f 3806 6.7 6.8 11.4 8.2 8.0 7.2 8.1 7.7 8.3 8.9 7.4 10.2 8.3 8.4 7.9 3807 4.9 5.8 6.5 6.0 6.2 6.0 6.3 6.8 7.0 7.1 6.1 7.3 7.1 6.5 6.0 3808 .e 6.0 8.1 6.9 9.3 8.4 6.3 10.7 6.9 6.9 7.2 6.6 6.9 7.6 .f 3809 6.0 4.9 5.6 5.3 6.5 7.7 6.6 7.9 8.4 .e 6.6 7.3 6.7 .f .f 3810 8.9 13.0 8.8 7.4 7.2 7.0 7.2 7.6 8.3 7.7 8.6 7.6 8.7 8.2 8.5 3811 7.9 10.9 .e 9.7 7.0 8.5 7.1 6.9 7.2 7.3 7.4 7.1 7.4 .f .f 3812 5.4 6.0 5.7 6.0 5.9 6.4 6.4 6.5 7.0 7.4 8.1 7.5 7.2 6.6 6.3 3813 .e 9.0 9.2 6.9 .e 7.4 7.7 7.5 7.3 8.0 7.5 7.6 7.0 .f .f 3814 .j 3815 .e 14.5 8.7 12.4 11.8 8.1 8.6 8.9 8.4 9.0 9.1 9.0 8.7 9.9 .f 3816 5.8 6.6 6.0 6.4 10.4 6.2 9.5 7.3 6.7 8.3 6.8 7.4 7.3 7.4 6.9 3817 .i 3818 .e .e .e 11.9 .h .e 9.5 9.1 8.4 7.6 10.5 11.7 7.9 .f .f 3819 5.2 5.4 5.8 5.9 5.2 6.7 .e 6.2 7.7 6.8 6.7 6.8 7.1 .f .f 3820 .e 9.3 8.1 17.8 8.9 8.9 7.7 9.1 8.7 7.7 7.9 8.9 9.2 9.4 .f
Appendix II 8 Table A-3. Individual Maternal Feed Consumption (g/day)a (page 3 of 5) Gestational Days Doseb Dam ID 0-5 5-6 6-7 7-8 8-9 9-10 10-11 11-12 12-13 13-14 14-15 15-16 16-17 5-10c 5-16d 10-17c 0-17 10000 3821 6.5 7.6 7.2 6.4 7.0 8.0 7.5 7.6 7.6 9.4 9.4 8.7 8.3 7.9 7.5 3822 5.1 5.3 5.8 7.3 5.8 7.0 6.8 6.0 9.6 6.9 7.2 6.8 7.4 6.8 6.3 3823 .i 20000 4801 4.2 5.2 6.2 5.9 5.3 6.1 5.9 5.7 6.1 6.4 7.2 6.5 8.0 6.0 5.6 4802 5.7 6.1 6.5 6.0 6.6 6.5 7.1 7.5 7.8 7.7 8.4 6.8 8.3 7.0 6.7 4803 .e .g .g .g 8.4 6.7 .g .g 8.8 10.2 7.7 7.4 9.9 10.2 .f 4804 5.1 5.0 6.1 5.6 5.5 5.5 5.5 6.4 6.2 6.6 6.9 7.1 8.9 6.0 5.9 4805 5.4 5.9 6.3 6.0 5.7 5.6 6.0 6.3 6.5 6.9 6.1 7.1 6.8 6.2 6.0 4806 .e 6.0 .g 6.1 6.4 6.8 6.2 .e 7.1 7.2 6.4 7.7 6.2 .f .f 4807 .e 7.8 9.3 .g .g 5.7 .g 6.7 7.4 7.9 7.6 8.4 7.0 8.6 .f 4808 4.8 5.6 6.0 5.7 5.6 5.5 5.7 6.7 6.7 6.5 7.2 7.0 7.0 6.2 5.8 4809 6.2 5.9 6.8 7.5 5.8 6.6 6.8 6.8 7.1 6.9 9.1 7.1 6.4 6.9 6.7 4810 .e 7.3 5.0 7.1 5.2 7.3 6.3 7.1 7.3 6.8 8.4 6.3 6.9 6.7 .f 4811 4.4 5.8 6.0 6.3 6.5 5.7 5.8 6.1 6.1 6.3 6.7 5.5 7.7 6.1 5.7 4812 4.0 4.9 4.7 5.1 5.0 5.1 5.1 5.0 5.2 5.3 7.7 5.9 6.5 5.4 5.0 4813 5.6 6.1 6.0 6.7 6.7 6.6 7.4 7.4 7.5 7.9 9.7 8.4 8.1 7.3 6.8 4814 5.3 9.8 .e 5.8 6.7 6.2 6.3 6.8 6.1 7.7 6.1 6.3 6.8 .f .f 4815 .i 4816 5.4 7.1 6.7 6.2 6.5 6.4 6.9 7.2 6.9 8.8 7.6 7.8 8.0 7.1 6.7 4817 5.4 5.7 7.0 6.4 5.9 6.0 5.7 6.8 6.3 8.2 6.4 7.2 7.1 6.5 6.2 4818 5.8 6.7 6.7 5.1 6.5 5.2 6.4 6.1 6.2 7.6 4.2 5.7 6.4 6.0 6.0 4819 4.9 5.0 4.3 5.3 5.2 5.6 6.7 5.5 7.0 5.2 4.4 4.9 4.1 5.4 5.2 4820 .h 6.2 .e .e .e .e 8.3 8.6 8.3 .e 8.1 7.4 7.1 .f .f 4821 .e 5.5 5.6 6.1 5.3 .h 5.2 7.1 5.1 6.9 6.9 6.7 7.1 .f .f 4822 6.1 6.5 6.8 8.0 7.8 6.2 7.7 6.9 7.6 6.9 7.2 7.8 8.7 7.2 7.0 4823 6.0 6.6 .g .e 6.2 7.6 5.7 7.3 7.6 5.6 7.0 6.1 6.9 .f .f 30000 5801 .i 5802 5.4 4.7 5.5 5.4 5.6 6.7 6.5 11.9 7.3 7.7 6.9 7.1 7.7 5.6 7.9 6.5 5803 5.3 5.9 5.9 5.7 5.6 6.1 6.1 6.7 6.6 7.2 7.1 6.7 8.2 5.8 6.9 6.1 5804 5.2 5.4 6.5 5.8 5.6 6.9 6.1 7.2 7.9 7.4 7.6 7.7 7.4 6.0 7.3 6.3 5805 .h 5.7 5.8 5.7 5.5 5.8 5.2 6.0 8.1 7.2 3.9 6.8 7.6 5.7 6.4 .f
Appendix II 9 Table A-3. Individual Maternal Feed Consumption (g/day)a (page 4 of 5) Gestational Days Doseb Dam ID 0-5 5-6 6-7 7-8 8-9 9-10 10-11 11-12 12-13 13-14 14-15 15-16 16-17 5-10c 5-16d 10-17c 0-17 30000 5806 .h 5.9 7.0 6.2 6.2 6.6 .h .e 8.3 7.2 6.4 7.0 8.0 6.4 .f .f 5807 7.6 6.0 6.3 6.8 6.6 6.2 5.9 7.9 7.4 7.4 8.1 7.2 7.1 6.4 7.3 7.1 5808 8.3 5.3 6.4 .h 5.0 6.8 6.2 7.1 6.2 7.4 8.1 6.5 .h .f .f .f 5809 .h 6.1 5.7 6.1 .h 6.1 5.5 8.4 .h 10.3 8.0 7.8 8.1 .f .f .f 5810 5.4 6.5 5.0 5.3 5.7 6.9 6.7 6.5 7.6 7.3 7.3 6.8 7.9 5.9 7.2 6.3 5811 5.6 6.3 7.9 7.0 7.0 6.0 6.9 7.3 8.2 8.1 8.3 8.6 9.0 6.8 8.1 7.0 5812 9.4 5.7 5.6 6.4 7.0 6.4 6.4 9.7 7.8 8.5 10.0 8.8 8.8 6.2 8.6 8.1 5813 .e .g 6.2 7.3 6.5 6.8 6.3 7.2 5.9 6.5 5.0 3.7 4.8 7.6 5.6 .f 5814 5.3 5.7 5.2 6.5 6.4 5.8 6.5 7.0 9.6 8.0 7.4 8.2 8.2 5.9 7.8 6.5 5815 10.4 6.0 6.2 5.8 6.2 5.7 5.9 6.9 7.9 7.8 7.8 7.0 6.5 6.0 7.1 7.7 5816 6.2 6.5 8.9 7.1 6.1 6.5 6.1 7.4 6.8 8.2 8.3 7.0 7.1 7.0 7.3 6.9 5817 .i 5818 4.7 6.3 4.6 6.3 5.8 5.7 6.7 7.2 6.6 7.7 5.6 .h 6.8 5.7 .f .f 5819 6.4 .e .e 7.4 6.4 6.2 .g 7.6 7.9 8.3 8.4 8.1 7.6 .f 8.4 .f 5820 9.0 5.1 5.4 6.9 5.3 5.6 5.6 6.3 11.4 8.5 7.2 7.2 7.1 5.7 7.6 7.4 5821 11.1 6.8 6.5 7.7 7.2 8.0 7.2 .g 7.3 7.8 8.1 8.6 8.5 7.2 8.9 9.0 5822 5.2 5.4 4.6 7.0 6.5 6.5 4.9 5.4 5.3 6.9 6.7 6.2 6.6 6.0 6.0 5.8 5823 5.7 6.7 5.3 6.6 5.8 6.1 6.2 7.2 6.9 8.7 8.8 8.1 8.3 6.1 7.7 6.7 5824 .e 4.7 4.7 3.9 5.0 5.2 4.7 6.8 6.2 6.3 6.6 3.7 4.2 4.7 5.5 .f 5825 5.1 5.9 6.7 6.2 5.9 5.5 5.8 6.4 7.7 7.1 9.0 7.4 6.7 6.0 7.2 6.2 5826 .e 6.2 7.4 5.8 6.2 6.6 6.3 8.7 8.6 9.4 9.1 7.7 7.5 6.4 8.2 .f 5827 4.5 4.5 5.6 5.0 4.9 5.6 5.3 6.4 6.8 7.5 7.4 6.9 7.3 5.1 6.8 5.6 5828 5.3 6.0 6.8 6.2 6.4 7.1 6.3 8.0 8.3 8.4 8.3 7.0 7.5 6.5 7.7 6.6 5829 10.0 5.7 .e .g 7.0 7.4 7.0 9.2 10.2 8.8 8.8 8.8 8.6 .f 8.8 .f 5830 7.2 6.6 .e 9.3 6.6 6.5 6.6 13.8 9.1 9.0 8.5 8.8 8.3 .f 9.2 .f 5831 .e 6.7 6.5 6.0 6.2 5.7 6.5 8.6 7.5 8.5 9.2 7.1 8.2 6.2 7.9 .f 5832 7.5 7.7 8.4 7.7 6.9 6.8 6.8 8.8 8.5 8.1 9.2 8.8 8.9 7.5 8.4 7.9 5833 .e .g 10.3 8.3 .e .e .g 9.6 9.4 9.6 7.9 6.9 6.8 .f 9.5 .f 5834 .h 4.5 .h 7.7 .h 6.0 6.0 .h .g 10.1 6.0 6.2 8.5 .f .f .f 5835 6.3 5.0 6.4 5.7 8.8 6.9 7.6 9.6 8.3 8.8 7.9 7.8 7.2 6.6 8.2 7.2 5836 .e 8.1 6.8 5.8 5.9 6.4 6.6 8.2 7.9 8.4 8.7 7.2 7.1 6.6 7.7 .f 5837 6.6 6.3 5.8 6.1 5.5 5.2 6.1 6.6 5.5 6.8 6.0 4.6 4.9 5.8 5.8 6.0 5838 .e .e 6.1 5.3 5.7 6.4 5.7 6.9 8.5 7.7 7.4 7.5 7.9 .f 7.4 .f
Appendix II 10 Table A-3. Individual Maternal Feed Consumption (g/day)a (page 5 of 5) aThese data represent the difference between the new feed jar weights (beginning weight; full feed jar) and the old feed jar (end weight; after the animal has fed for the measurement interval) weights divided by the number of days in the measurement interval. bMg/m3 of gasoline MTBE vapor condensate. cThis endpoint was only calculated for the 0 and 30000 mg/m3 dose groups. dThis endpoint was only calculated for the 0, 2000, 10000 and 20000 mg/m3 dose groups. eFeed spilled therefore the feed weight was excluded. fInterim feed consumption value(s) are missing and therefore the overall feed consumption value could not be calculated. gFeed consumption value was a statistical outlier and therefore it was excluded. hFeed was contaminated therefore the feed weight was excluded. iFemale was not pregnant. jFemale was removed due to a preexisting condition. At necropsy she was found to have an undescended testis on the right and seminal vesicles and prostate to the right of the vagina and cervix. 
Appendix II 11 

Table A-4. Individual Embryo/Fetal Data (page 1 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

0 1801 11 1 A L 1 F 1.0230 

 2 A L 2 M 0.8182 

 3 A L 3 M 0.9328 

 4 D L 0.7402 

 5 E R 

 6 A R 4 M 0.9507 

 7 A R 5 M 0.9290 

 8 A R 6 F 0.9828 

 9 A R 7 F 1.0268 

 10 A R 8 M 0.9286 

 11 A R 9 M 0.9976 External Variation Hematoma: Head 

 External Variation Hematoma: Neck 

 1802 13 1 A L 1 F 1.0746 

 2 A L 2 M 1.0913 

 3 A L 3 F 1.0557 

 4 A L 4 M 1.0646 

 5 A R 5 M 1.0013 

 6 A R 6 F 1.0405 

 7 A R 7 F 0.9931 

 8 A R 8 F 1.0460 

 9 A R 9 M 1.1404 

 10 A R 10 M 1.1569 

 11 A R 11 M 1.0598 

 12 A R 12 F 1.0618 

 13 A R 13 F 1.0505 

 1803 9 1 A L 1 F 1.2866 

 2 A L 2 F 1.4021 

 3 E L 

 4 A R 3 M 1.3324 

 5 A R 4 F 1.2360 

 6 A R 5 F 0.9690 External Malformation Cleft Palate 

 7 A R 6 F 1.1523 External Variation Hematoma: Head 

 8 A R 7 F 1.2401 

 9 A R 8 M 1.3432 

 1804 14 1 A L 1 F 1.0263 

 2 A L 2 M 1.0068 

 3 A L 3 M 0.9753 

 4 A L 4 F 0.8615 

 5 A L 5 F 0.9291 

 6 A R 6 M 1.0035 

 7 A R 7 M 0.9158 

 8 A R 8 M 0.9942 

 9 A R 9 F 0.9321 

 10 A R 10 F 0.9239 

 11 A R 11 M 0.9972 

 12 A R 12 F 0.9071 

 13 A R 13 F 0.9282 

 1805 13 1 A L 1 M 1.0623 

 2 A L 2 M 1.0939 

 3 A L 3 M 1.0992 

 4 A L 4 M 1.0797 

 5 A L 5 F 1.0217 

 6 A R 6 F 1.0826 

 7 A R 7 F 1.0288 

 8 A R 8 M 1.0531 

 9 A R 9 F 1.0119 

 10 A R 10 M 1.0624 

 11 A R 11 F 0.8523 

 12 A R 12 F 1.0232 
Appendix II 12 

Table A-4. Individual Embryo/Fetal Data (page 2 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

0 1806 14 1 A L 1 F 1.0370 

 2 A L 2 M 1.0681 

 3 A L 3 M 0.8841 

 4 A L 4 M 0.9099 

 5 A L 5 M 0.9751 

 6 A L 6 M 0.7932 

 7 A L 7 M 0.9739 

 8 A L 8 M 1.0688 

 9 A R 9 M 1.1047 

 10 A R 10 M 0.9852 

 11 A R 11 F 0.9760 

 12 A R 12 M 1.0491 

 13 A R 13 F 1.0917 

 1807 15 1 A L 1 M 0.8745 

 2 A L 2 F 0.9240 

 3 A L 3 M 0.8271 

 4 A L 4 F 0.9596 

 5 A L 5 M 0.8050 

 6 A L 6 M 0.9051 

 7 A L 7 M 0.8972 

 8 A L 8 M 0.9840 

 9 A R 9 M 0.9552 

 10 A R 10 M 0.9733 

 11 E R 

 12 A R 11 M 1.0288 

 13 A R 12 F 0.9371 

 14 A R 13 F 0.8945 

 15 A R 14 M 0.9640 

 1808 15 1 A L 1 F 0.8116 

 2 A L 2 M 0.8444 

 3 A L 3 M 0.8401 

 4 A L 4 M 0.7738 

 5 A L 5 F 0.7672 

 6 A L 6 F 0.8215 

 7 A R 7 F 0.8106 

 8 A R 8 M 0.7823 

 9 A R 9 M 0.7679 

 10 A R 10 M 0.6397 

 11 A R 11 F 0.7671 

 12 A R 12 M 0.8271 

 13 A R 13 M 0.8018 

 14 A R 14 M 0.7566 

 15 A R 15 M 0.8540 

 1809 11 1 A L 1 F 0.9641 

 2 A L 2 F 1.0304 

 3 A R 3 M 0.6548 

 4 A R 4 M 0.8226 

 5 A R 5 F 0.8699 

 6 A R 6 F 0.8221 

 7 A R 7 M 0.8814 

 8 A R 8 M 0.9828 

 9 A R 9 F 0.8574 

 10 A R 10 F 0.8405 

 11 A R 11 F 0.8094 
Appendix II 13 

Table A-4. Individual Embryo/Fetal Data (page 3 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

0 1810 13 1 A L 1 M 1.1877 

 2 A L 2 M 0.9171 

 3 A L 3 M 1.1916 

 4 A L 4 F 1.1147 

 5 E R 

 6 E R 

 7 A R 5 F 1.1019 

 8 A R 6 F 1.2054 

 9 A R 7 F 1.0496 

 10 A R 8 F 1.1505 

 11 E R 

 12 A R 9 M 1.0525 

 1811 14 1 A L 1 M 1.1393 

 2 A L 2 F 1.0167 

 3 A L 3 M 1.0642 

 4 A L 4 M 1.0878 

 5 A L 5 F 1.0595 

 6 A L 6 M 1.0034 

 7 A L 7 M 0.9544 

 8 A L 8 M 0.9429 

 9 A L 9 M 1.0414 

 10 A R 10 M 1.1475 

 11 A R 11 M 1.0808 

 12 A R 12 F 1.0640 

 13 A R 13 F 1.0829 

 14 A R 14 M 1.0891 

 1812 13 1 A L 1 F 0.9006 

 2 A L 2 M 0.8712 

 3 A L 3 F 0.8832 

 4 A R 4 F 0.8264 

 5 A R 5 F 0.8169 

 6 A R 6 F 0.7940 

 7 A R 7 M 0.8558 

 8 A R 8 M 0.8438 

 9 A R 9 F 0.8537 

 10 A R 10 F 0.7710 

 11 A R 11 F 0.8807 

 12 A R 12 M 0.8740 

 13 A R 13 M 0.8937 

 1813 11 1 A L 1 F 1.0101 

 2 A L 2 M 1.1114 

 3 A L 3 M 1.1098 

 4 A L 4 M 1.0110 

 5 A L 5 M 0.9292 

 6 A L 6 F 1.0585 

 7 A L 7 M 1.0834 

 8 A R 8 M 1.1358 

 9 E R 

 10 A R 9 F 1.0958 

 11 A R 10 F 1.0459 
Appendix II 14 

Table A-4. Individual Embryo/Fetal Data (page 4 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

0 1814 14 1 A L 1 F 0.9528 

 2 A L 2 F 0.7076 

 3 A L 3 F 0.9589 

 4 A L 4 F 1.0443 

 5 A L 5 M 1.0409 

 6 A L 6 F 1.0072 

 7 A R 7 M 0.9022 

 8 A R 8 F 0.9146 

 9 A R 9 F 0.8631 

 10 D R 0.6018 

 11 A R 10 F 0.9350 

 12 A R 11 M 0.9835 

 13 E R 

 14 A R 12 F 1.0240 

 1815 11 1 A L 1 M 1.0836 

 2 A L 2 F 0.9789 

 3 E L 

 4 A L 3 M 1.0703 

 5 A L 4 M 0.9151 

 6 A L 5 M 1.0118 

 7 A L 6 F 1.1307 

 8 A R 7 F 1.0776 

 9 A R 8 M 1.0655 

 10 A R 9 F 1.1202 

 11 A R 10 F 0.9812 

 12 A R 11 M 1.1028 

 1816 14 1 A L 1 M 0.9686 External Malformation Cleft Palate 

 2 A L 2 M 1.0881 

 3 A L 3 M 1.0086 

 4 A L 4 F 0.9104 

 5 A L 5 F 0.9647 

 6 A L 6 M 1.1311 

 7 A L 7 F 1.1062 

 8 A R 8 F 1.0862 

 9 A R 9 F 1.0008 

 10 A R 10 F 1.0492 

 11 A R 11 F 1.0072 

 12 A R 12 M 1.1214 

 13 A R 13 M 1.1400 

 14 A R 14 M 1.0859 

 1817 11 1 A L 1 M 0.8516 

 2 A L 2 M 0.8587 

 3 A L 3 M 0.8686 

 4 A L 4 F 0.8578 

 5 A L 5 F 0.9120 

 6 A L 6 F 0.8655 

 7 A R 7 F 0.8314 

 8 A R 8 F 0.9139 

 9 A R 9 F 1.0210 

 10 E R 

 11 A R 10 M 0.7935 
Appendix II 15 

Table A-4. Individual Embryo/Fetal Data (page 5 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

0 1818 17 1 A L 1 M 1.3283 

 2 A L 2 M 1.4374 

 3 A L 3 F 1.2843 

 4 A L 4 F 1.3751 

 5 A L 5 M 1.4098 

 6 E R 

 7 A R 6 F 1.3769 

 8 A R 7 F 1.1389 

 9 D R 0.8652 

 10 A R 8 M 1.2370 

 11 A R 9 F 0.9656 

 12 A R 10 F 1.1105 

 13 A R 11 F 1.1893 

 14 A R 12 F 1.3430 

 1819 13 1 A L 1 F 1.2033 

 2 A L 2 F 1.2014 

 3 A L 3 M 1.2734 

 4 A L 4 M 1.2249 

 5 A L 5 M 1.2560 

 6 A L 6 F 1.2349 

 7 A L 7 M 1.3133 

 8 A L 8 M 1.2207 

 9 A R 9 M 1.1921 

 10 A R 10 M 1.2161 

 11 A R 11 M 1.2267 

 12 A R 12 F 1.1668 

 13 A R 13 F 1.2489 

 1820 15 1 A L 1 M 1.1172 

 2 A L 2 M 0.9227 

 3 A L 3 F 0.9747 

 4 E L 

 5 E L 

 6 A L 4 F 0.8975 

 7 A L 5 F 0.9357 

 8 A R 6 M 0.9353 External Variation Hematoma: Shoulder 

 9 A R 7 M 0.9363 

 10 A R 8 M 0.9574 

 11 A R 9 F 0.9115 

 12 A R 10 M 0.9384 

 13 A R 11 F 0.9389 

 14 A R 12 F 0.8823 

 15 A R 13 F 0.9283 

 16 A R 14 F 0.7267 

 1821 11 1 A L 1 M 0.8618 

 2 A L 2 M 0.9622 

 3 A L 3 F 0.9537 

 4 A R 4 M 0.7376 

 5 A R 5 M 0.8339 

 6 A R 6 F 0.8517 

 7 A R 7 M 0.8706 

 8 A R 8 M 0.9207 

 9 A R 9 F 0.8109 

 10 A R 10 M 0.7936 

 11 A R 11 F 0.9996 
Appendix II 16 

Table A-4. Individual Embryo/Fetal Data (page 6 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

0 1822 12 1 A L 1 F 0.9341 

 2 A L 2 F 0.9481 

 3 A L 3 M 0.9897 

 4 A L 4 M 1.0243 

 5 A L 5 M 1.0367 

 6 A R 6 F 0.9537 

 7 A R 7 F 0.8929 

 8 A R 8 M 0.8955 

 9 A R 9 F 0.8876 

 10 A R 10 F 0.9153 

 11 A R 11 M 0.9270 

 12 A R 12 F 0.9892 

 1823 14 1 A L 1 F 0.7610 

 2 A L 2 M 0.9371 

 3 A L 3 F 1.0011 

 4 E L 

 5 A L 4 F 0.9726 

 6 A R 5 F 0.8709 

 7 A R 6 F 0.9728 

 8 A R 7 F 0.9841 

 9 A R 8 M 0.9371 

 10 A R 9 F 0.9246 

 11 A R 10 F 0.7944 

 12 A R 11 M 0.9476 

 13 A R 12 M 0.8361 

 14 A R 13 M 0.9707 

2000 2801 5 1 A R 1 F 1.3441 

 2802 8 1 A L 1 M 1.2708 

 2 A L 2 F 1.0697 

 3 E L 

 4 E L 

 5 E L 

 6 A R 3 M 1.2216 

 7 A R 4 M 1.2408 

 8 E R 

 9 A R 5 F 1.0764 

 10 A R 6 M 1.1545 

 11 A R 7 F 1.0262 

 12 E R 

 13 A R 8 F 1.0773 

 2803 15 1 A L 1 M 0.9750 

 2 A L 2 M 1.0125 

 3 A L 3 F 1.0308 

 4 A L 4 M 1.0001 

 5 A L 5 M 1.0323 

 6 A L 6 F 0.9611 

 7 A R 7 M 1.0954 External Variation Hematoma: Head 

 External Variation Hematoma: Neck 

 8 A R 8 M 1.1073 

 9 A R 9 F 0.9910 

 10 A R 10 M 0.9514 

 11 A R 11 M 0.9946 

 12 A R 12 M 1.0013 

 13 A R 13 F 1.0459 

 14 A R 14 F 0.9746 

 15 A R 15 F 1.0812 
Appendix II 17 

Table A-4. Individual Embryo/Fetal Data (page 7 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

2000 2804 12 1 A L 1 F 0.9064 

 2 A L 2 M 0.9034 

 3 A R 3 M 0.9715 

 4 A R 4 F 0.8306 

 5 A R 5 F 0.7990 

 6 A R 6 F 0.8979 

 7 A R 7 M 0.7550 

 8 A R 8 M 0.8960 

 9 A R 9 F 0.7931 

 10 A R 10 F 0.7344 

 11 A R 11 F 0.8566 

 12 A R 12 M 0.9062 

 2805 12 1 A L 1 M 0.9858 

 2 A L 2 F 0.9488 

 3 A L 3 F 0.7516 

 4 A L 4 M 0.9525 

 5 A R 5 F 0.8988 

 6 A R 6 M 0.9142 

 7 A R 7 M 1.0188 

 8 A R 8 F 0.8397 

 9 A R 9 M 0.7913 

 10 A R 10 M 0.8964 

 11 A R 11 F 0.8909 

 12 A R 12 M 1.0129 

 2806 12 1 A L 1 M 1.0891 

 2 A L 2 M 1.0178 

 3 A L 3 M 1.0216 

 4 A R 4 F 0.9649 

 5 A R 5 M 0.9381 

 6 A R 6 M 0.9603 

 7 A R 7 F 0.8702 

 8 A R 8 M 1.0281 

 9 A R 9 F 0.9887 

 10 A R 10 M 1.0687 

 11 A R 11 M 1.0483 

 12 A R 12 M 0.9483 

 2807 12 1 A L 1 M 1.0771 

 2 A L 2 M 0.8771 

 3 E L 

 4 A L 3 M 1.1134 

 5 A L 4 M 1.0197 

 6 A R 5 M 1.0057 

 7 A R 6 F 0.8473 

 8 A R 7 F 0.8830 

 9 A R 8 M 1.0132 

 10 A R 9 F 0.8436 

 11 E R . 

 12 A R 10 M 1.0088 

 2808 13 1 A L 1 M 0.8984 

 2 M L 

 3 A L 2 M 0.9015 

 4 A L 3 F 0.9677 

 5 A L 4 M 0.9335 

 6 M L 

 7 A L 5 M 0.9938 

 8 A L 6 M 0.9303 

 9 M R 

 10 A R 7 M 1.1087 

 11 E R 

 12 E R 

 13 A R 8 F 1.0222 
Appendix II 18 

Table A-4. Individual Embryo/Fetal Data (page 8 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

2000 2809 10 1 A L 1 M 1.0041 

 2 A L 2 F 1.0047 

 3 E L 

 4 A L 3 F 0.9698 

 5 A L 4 M 0.9814 

 6 A L 5 M 0.9031 

 7 A R 6 M 1.0715 

 8 E R 

 9 A R 7 F 1.0581 

 10 A R 8 F 1.0225 

 11 A R 9 F 0.8569 

 12 A R 10 F 0.9546 

 13 A R 11 M 0.9146 

 2810 10 1 A L 1 F 1.0928 

 2 A L 2 M 1.0999 

 3 A L 3 F 1.0128 

 4 A R 4 M 1.1283 

 5 A R 5 F 1.0145 

 6 A R 6 F 0.9308 

 7 A R 7 M 1.0088 

 8 A R 8 F 0.9268 

 9 A R 9 M 1.0164 

 10 A R 10 M 0.9720 

 2811 14 1 A L 1 F 1.0482 

 2 A L 2 F 0.9048 

 3 A L 3 F 0.9513 

 4 A L 4 F 0.9646 

 5 A L 5 M 0.9417 

 6 A L 6 M 0.7961 

 7 A L 7 M 0.9538 

 8 A L 8 F 0.8648 

 9 A R 9 F 0.8361 

 10 A R 10 F 0.9768 

 11 A R 11 M 0.9976 

 12 A R 12 M 0.9588 

 13 A R 13 M 0.9767 

 2812 14 1 A L 1 M 1.1579 

 2 A L 2 F 1.0919 

 3 A L 3 F 1.0422 

 4 A L 4 F 1.0483 

 5 A L 5 M 0.9578 

 6 A L 6 M 1.0596 

 7 A L 7 F 1.0260 

 8 A L 8 M 1.1331 

 9 A R 9 F 1.0548 

 10 A R 10 M 1.1496 

 11 A R 11 F 1.0310 

 12 A R 12 M 1.0993 

 13 A R 13 F 1.0189 

 14 A R 14 F 1.0590 

 2813 10 1 I L 

 2 I L 

 3 I L 

 4 I R 

 5 I R 

 6 I R 

 7 I R 

 8 I R 

 9 I R 

 10 I R 
Appendix II 19 

Table A-4. Individual Embryo/Fetal Data (page 9 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

2000 2814 11 1 A L 1 M 1.0360 

 2 A L 2 M 0.9772 

 3 A L 3 M 0.8825 

 4 A L 4 F 0.9772 

 5 A L 5 M 0.9588 

 6 E L 

 7 A L 6 F 1.0073 

 8 A R 7 F 0.9526 

 9 A R 8 F 1.0928 

 10 A R 9 F 1.0102 

 11 A R 10 F 1.0398 

 2815 16 1 A L 1 F 1.0205 

 2 A L 2 F 1.0379 

 3 A L 3 F 0.9504 

 4 A L 4 M 1.0584 

 5 A L 5 F 1.1114 

 6 A L 6 F 0.8976 

 7 A L 7 F 1.0575 

 8 A L 8 F 1.0156 

 9 A L 9 M 1.0038 

 10 A R 10 F 0.9891 

 11 A R 11 M 1.1001 

 12 A R 12 M 1.0271 

 13 A R 13 M 1.1058 

 2816 12 1 A L 1 M 1.1100 

 2 A L 2 F 1.0718 

 3 A L 3 M 1.0676 

 4 A L 4 F 1.0803 

 5 A L 5 M 1.1129 

 6 A R 6 F 1.1096 

 7 A R 7 F 0.9815 

 8 A R 8 F 1.0332 

 9 A R 9 F 0.9981 

 10 A R 10 F 1.1400 

 11 A R 11 F 0.9800 

 12 A R 12 M 0.9989 

 2817 15 1 A L 1 F 1.0393 

 2 A L 2 F 0.9766 

 3 A L 3 M 1.1003 

 4 A L 4 F 1.0763 

 5 A R 5 F 1.0411 

 6 A R 6 F 0.9787 

 7 A R 7 F 0.9803 

 8 A R 8 M 1.0243 

 9 A R 9 M 1.0327 

 10 A R 10 F 0.9913 

 11 A R 11 F 1.0011 

 12 A R 12 F 0.9916 
Appendix II 20 

Table A-4. Individual Embryo/Fetal Data (page 10 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

2000 2818 17 1 A L 1 F 0.9018 

 2 A L 2 M 0.9189 

 3 A L 3 M 1.0189 

 4 A L 4 F 0.9339 

 5 A L 5 F 0.7564 

 6 A L 6 F 0.9032 

 7 A L 7 M 0.8642 External Malformation Cleft Palate 

 8 A L 8 F 0.9189 

 9 A L 9 M 1.0005 

 10 A L 10 M 0.9558 

 11 A R 11 F 0.9258 

 12 A R 12 M 0.9915 

 13 A R 13 F 0.9614 

 14 A R 14 F 0.8635 

 15 A R 15 F 0.8936 

 16 A R 16 F 0.8928 

 2819 13 1 A L 1 F 1.0275 

 2 A L 2 F 1.1046 

 3 A L 3 M 1.0580 

 4 A R 4 M 1.0291 

 5 A R 5 F 0.7359 External Malformation Encephalocele 

 6 A R 6 M 0.8896 

 7 A R 7 M 0.9365 

 8 A R 8 M 0.9639 

 9 A R 9 F 0.9304 

 10 A R 10 M 1.0039 

 11 A R 11 M 1.0009 

 12 A R 12 F 0.9925 

 13 A R 13 M 1.0325 

 2820 14 1 A L 1 F 1.1862 

 2 A L 2 M 1.0684 

 3 A L 3 M 0.9071 

 4 A L 4 F 1.2382 

 5 A R 5 F 1.0283 

 6 A R 6 F 1.0491 

 7 A R 7 F 1.0592 

 8 E R 

 9 A R 8 F 0.9977 

 10 A R 9 F 1.0505 

 11 A R 10 F 0.8839 

 12 A R 11 M 0.9944 

 13 A R 12 M 0.7045 

 14 A R 13 F 0.9805 

 2821 .g 

 2822 11 1 A L 1 F 0.9312 

 2 A L 2 F 0.9493 External Variation Hematoma: Face 

 3 A L 3 F 1.0554 

 4 A L 4 F 1.0212 

 5 A R 5 M 1.0618 

 6 E R 

 7 A R 6 F 1.0410 External Variation Hematoma: Face 

 8 A R 7 M 1.0158 

 9 A R 8 F 1.0331 

 10 A R 9 M 1.0376 

 11 A R 10 M 0.9412 
Appendix II 21 

Table A-4. Individual Embryo/Fetal Data (page 11 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

2000 2823 12 1 A L 1 F 0.9744 

 2 A L 2 F 1.0834 

 3 A L 3 M 1.0539 

 4 E L 

 5 A L 4 F 1.0137 

 6 A R 5 M 1.1048 

 7 A R 6 F 0.9936 

 8 A R 7 M 1.0680 

 9 A R 8 M 1.0025 

 10 A R 9 M 1.0029 

 11 A R 10 M 1.0112 

 12 A R 11 F 0.9788 

10000 3801 13 1 A L 1 M 1.0190 

 2 A L 2 M 0.9014 

 3 A L 3 M 0.9821 

 4 A L 4 M 1.0398 

 5 A L 5 M 1.0434 

 6 A L 6 F 0.8964 

 7 A L 7 F 0.9460 

 8 A R 8 M 1.0947 

 9 A R 9 M 1.0239 

 10 A R 10 M 0.9811 

 11 E R 

 12 A R 11 M 0.9961 

 3802 .g 

 3803 10 1 A L 1 F 1.1517 

 2 A L 2 M 1.0631 

 3 A L 3 F 1.1021 

 4 E L 

 5 A L 4 F 1.1125 

 6 A L 5 M 1.2200 

 7 A R 6 F 1.0961 

 8 A R 7 F 1.0464 

 9 A R 8 F 1.0687 

 10 A R 9 M 1.2010 

 11 A R 10 F 1.1963 

 12 A R 11 M 1.2033 

 13 E R 

 3804 14 1 A L 1 M 0.9328 

 2 A L 2 M 0.9306 

 3 A L 3 F 0.8937 

 4 A L 4 F 0.9386 

 5 L R 

 6 A R 5 M 0.9326 

 7 A R 6 M 0.9338 

 8 A R 7 M 0.8966 

 9 A R 8 M 0.9382 

 10 A R 9 M 0.9291 

 11 A R 10 M 0.9202 

 12 A R 11 F 0.9163 
Appendix II 22 

Table A-4. Individual Embryo/Fetal Data (page 12 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

10000 3805 16 1 A L 1 F 0.8832 

 2 A L 2 F 0.9752 

 3 A L 3 M 1.0583 

 4 A L 4 M 0.8836 

 5 E R 

 6 D R 0.7638 

 7 A R 5 F 0.9635 

 8 A R 6 M 0.8553 

 9 A R 7 F 0.8790 

 10 A R 8 F 0.8643 

 11 A R 9 M 0.9115 

 12 A R 10 M 0.9509 

 13 A R 11 F 0.8660 

 14 A R 12 F 0.8833 

 3806 13 1 A L 1 F 1.1007 

 2 A L 2 M 1.0647 

 3 A L 3 F 1.0466 

 4 A L 4 M 1.0508 

 5 A L 5 F 1.1125 

 6 A L 6 M 1.1215 

 7 A L 7 M 1.0254 

 8 A L 8 F 1.1635 

 9 A R 9 M 1.2134 

 10 A R 10 F 1.1405 

 11 A R 11 M 1.2279 

 12 A R 12 F 1.1768 

 13 A R 13 F 1.2030 

 3807 12 1 A L 1 F 0.8125 

 2 A L 2 F 0.8706 

 3 A L 3 F 0.7146 

 4 A L 4 F 0.7455 

 5 A L 5 F 0.6843 

 6 A R 6 M 0.7882 

 7 A R 7 F 0.7540 

 8 A R 8 F 0.7794 

 9 A R 9 F 0.7171 

 10 A R 10 M 0.7736 

 11 A R 11 M 0.7202 

 12 A R 12 M 0.7913 

 3808 11 1 A L 1 M 0.9736 

 2 A L 2 F 0.9106 

 3 A L 3 M 0.9582 

 4 A L 4 M 0.9339 

 5 A R 5 M 0.9355 

 6 A R 6 F 0.8832 

 7 A R 7 M 0.9395 

 8 A R 8 F 0.9138 

 9 M R 

 10 A R 9 M 0.8939 

 11 M R 
Appendix II 23 

Table A-4. Individual Embryo/Fetal Data (page 13 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

10000 3809 13 1 A L 1 F 0.7510 

 2 A L 2 F 0.8011 

 3 A L 3 M 0.8512 

 4 A L 4 F 0.9113 

 5 A L 5 M 0.8740 

 6 A R 6 F 0.8957 

 7 A R 7 M 0.8702 

 8 A R 8 M 0.9312 External Variation Hematoma: Neck 

 9 A R 9 M 0.9074 

 10 A R 10 F 0.8759 

 11 A R 11 M 0.8169 

 12 A R 12 M 0.8717 

 13 A R 13 M 0.8925 

 3810 12 1 A L 1 F 0.9400 

 2 A L 2 F 0.8910 

 3 A L 3 M 1.0533 

 4 A L 4 M 0.9740 

 5 A L 5 F 0.9930 

 6 A L 6 F 0.9413 

 7 A R 7 F 0.9848 

 8 A R 8 M 1.0769 

 9 A R 9 F 0.9693 

 10 A R 10 M 1.0352 

 11 A R 11 M 1.0835 

 12 A R 12 F 0.9862 

 3811 11 1 A L 1 M 0.9645 

 2 A L 2 M 1.0063 

 3 A L 3 F 0.9305 

 4 A L 4 F 0.8759 

 5 A R 5 M 0.9009 

 6 A R 6 M 0.8406 

 7 A R 7 M 0.8920 

 8 A R 8 M 0.5587 

 9 A R 9 F 0.8932 

 10 A R 10 F 0.9297 

 11 A R 11 M 0.9312 

 3812 13 1 A L 1 M 1.0739 

 2 A L 2 M 0.9977 

 3 A L 3 F 1.0568 

 4 A L 4 F 0.9341 

 5 A L 5 F 0.8089 

 6 A L 6 F 1.0368 

 7 A L 7 M 1.0440 

 8 A R 8 F 1.0519 

 9 A R 9 F 0.9655 

 10 A R 10 F 1.0877 

 11 A R 11 F 1.0286 

 12 A R 12 F 1.0178 

 13 A R 13 M 0.9960 

 3813 12 1 A L 1 M 0.9396 

 2 A L 2 M 0.9545 

 3 E L 

 4 A L 3 M 0.9843 

 5 A L 4 F 0.9474 

 6 A L 5 M 0.9391 

 7 A R 6 M 0.9248 

 8 A R 7 F 0.9039 

 9 A R 8 F 0.9342 

 10 A R 9 F 0.9293 

 11 A R 10 F 0.9427 

 12 A R 11 F 0.9326 
Appendix II 24 

Table A-4. Individual Embryo/Fetal Data (page 14 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

10000 3814 .h 

 3815 11 1 A L 1 F 1.1360 

 2 A L 2 M 1.1999 

 3 A L 3 F 1.1700 

 4 A L 4 M 1.1825 

 5 A L 5 M 1.1779 

 6 A L 6 M 1.1906 

 7 A R 7 M 1.1756 

 8 A R 8 M 1.1893 

 9 A R 9 M 1.2653 

 10 A R 10 M 1.1124 

 11 A R 11 M 1.1893 

 3816 15 1 A L 1 M 0.8593 

 2 A L 2 F 0.8340 

 3 A L 3 F 0.8706 

 4 A L 4 F 0.8719 

 5 A L 5 F 0.8671 

 6 A L 6 M 0.8532 

 7 A L 7 F 0.8176 

 8 A R 8 M 0.9453 

 9 A R 9 M 0.8392 External Malformation Cleft Palate 

 10 A R 10 M 0.8336 

 11 A R 11 F 0.8685 

 12 A R 12 F 0.8623 

 13 A R 13 M 0.9595 

 14 M R 

 15 A R 14 F 0.8344 

 3817 .g 

 3818 14 1 A L 1 F 0.8906 

 2 A L 2 F 0.8837 

 3 A L 3 M 1.0012 

 4 A R 4 M 0.9925 

 5 A R 5 F 0.9106 

 6 A R 6 F 0.8052 

 7 A R 7 M 0.9135 

 8 A R 8 M 1.0314 

 9 A R 9 M 0.9259 

 10 A R 10 F 0.8523 

 11 A R 11 F 0.8937 

 3819 14 1 A L 1 M 0.8560 

 2 A L 2 F 0.8368 

 3 A L 3 F 0.8758 

 4 A L 4 F 0.9340 

 5 A L 5 M 0.9200 

 6 A L 6 F 0.8570 

 7 A L 7 M 0.9478 

 8 A L 8 M 0.9177 

 9 E R 

 10 A R 9 F 0.9978 

 11 A R 10 F 0.9447 

 12 A R 11 M 1.0698 

 13 A R 12 F 0.9054 
Appendix II 25 

Table A-4. Individual Embryo/Fetal Data (page 15 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

10000 3820 13 1 A L 1 F 0.7350 

 2 A L 2 M 0.7557 

 3 A L 3 F 0.8625 

 4 A L 4 M 0.9689 

 5 A L 5 F 0.8864 

 6 A L 6 F 0.9464 

 7 A L 7 M 0.9343 

 8 A R 8 F 0.9803 

 9 A R 9 F 0.8394 

 10 A R 10 M 1.0069 

 11 A R 11 M 0.9770 

 12 A R 12 F 0.9931 

 3821 .i 1 D L 0.7329 

 2 A L 1 M 0.9617 

 3 A L 2 M 0.8419 

 4 A L 3 M 0.8902 

 5 A L 4 F 0.9598 

 6 A L 5 M 0.9075 

 7 E R 

 8 A R 6 F 0.9211 

 9 A R 7 F 0.9019 

 10 A R 8 M 0.7350 

 11 A R 9 M 0.8225 

 12 L R 

 13 A R 10 M 0.7931 

 14 A R 11 M 0.8594 

 15 A R 12 M 0.8169 

 16 A R 13 F 0.9058 

 3822 13 1 A L 1 M 0.8384 

 2 E L 

 3 A L 2 M 0.8672 

 4 A L 3 F 0.8362 

 5 A L 4 F 0.9295 

 6 E L 

 7 A R 5 M 0.9220 

 8 A R 6 M 0.7331 

 9 A R 7 F 0.8611 

 10 A R 8 M 0.8935 

 11 A R 9 M 0.8065 

 12 A R 10 M 0.9002 

 13 A R 11 M 0.8964 

 14 A R 12 F 0.9067 

 15 A R 13 F 0.7866 External Variation Abnormal Rugae in Midline of Palate 

 3823 .g 

20000 4801 15 1 A L 1 M 0.7756 External Variation Hematoma: Neck 

 2 A L 2 M 0.9303 

 3 A L 3 F 0.8679 

 4 A L 4 F 0.8982 

 5 A L 5 M 0.8411 

 6 A L 6 F 0.9145 

 7 A L 7 M 0.9662 

 8 A L 8 M 0.9387 

 9 A L 9 F 0.7659 

 10 A L 10 F 0.8141 

 11 A R 11 F 0.9080 

 12 A R 12 F 0.9201 

 13 A R 13 F 0.8216 
Appendix II 26 

Table A-4. Individual Embryo/Fetal Data (page 16 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

20000 4802 13 1 A L 1 M 1.0719 

 2 A L 2 M 1.0172 

 3 E L 

 4 A L 3 F 0.9307 External Variation Hematoma: Neck 

 5 A L 4 F 0.7838 

 6 A L 5 F 1.0347 

 7 A R 6 F 0.9325 

 8 A R 7 F 0.9266 

 9 A R 8 F 1.0504 

 10 A R 9 F 0.9771 

 11 A R 10 F 1.0003 

 12 A R 11 M 0.9209 

 13 A R 12 F 1.0126 

 4803 12 1 A L 1 F 1.1729 

 2 A L 2 M 1.1987 

 3 A L 3 M 1.0925 

 4 A L 4 M 1.1984 

 5 A L 5 F 1.1336 

 6 A L 6 F 1.1188 

 7 A L 7 F 1.1314 

 8 A R 8 F 1.1490 

 9 A R 9 F 1.0659 

 10 A R 10 F 1.1253 

 11 A R 11 M 1.1589 

 12 A R 12 M 1.0840 

 13 A R 13 M 1.1359 

 4804 15 1 A L 1 M 1.1320 

 2 A L 2 M 1.0061 

 3 A L 3 M 1.0438 

 4 A L 4 F 1.0220 

 5 A L 5 M 1.0451 

 6 A R 6 F 0.9857 

 7 A R 7 M 0.9875 

 8 A R 8 M 0.9954 

 9 A R 9 F 0.9630 

 10 A R 10 F 0.9950 

 11 A R 11 F 0.7918 

 12 A R 12 M 1.0053 

 13 M R 

 14 A R 13 M 0.9716 

 4805 13 1 A L 1 M 0.8523 

 2 A L 2 F 0.8314 

 3 A L 3 F 0.9040 

 4 A L 4 F 0.8392 

 5 A L 5 M 0.7989 

 6 A L 6 M 0.8065 

 7 A L 7 M 0.8913 

 8 A R 8 M 0.9045 

 9 A R 9 M 0.9049 

 10 A R 10 F 0.9584 

 11 A R 11 M 0.9496 

 12 A R 12 F 0.8322 

 13 A R 13 M 0.9007 
Appendix II 27 

Table A-4. Individual Embryo/Fetal Data (page 17 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

20000 4806 13 1 A L 1 F 0.9073 

 2 A L 2 M 0.8205 

 3 A L 3 F 0.9315 

 4 A L 4 M 0.9512 

 5 A L 5 F 0.6950 

 6 A L 6 M 0.9079 

 7 A L 7 F 0.9127 

 8 A L 8 F 0.8739 

 9 A R 9 M 0.9375 

 10 A R 10 M 0.9311 

 11 A R 11 M 0.8928 

 12 A R 12 M 0.8862 

 13 A R 13 F 0.8459 

 4807 13 1 A L 1 M 0.8860 

 2 A L 2 F 0.9351 

 3 A L 3 F 0.9293 

 4 A L 4 M 0.9260 

 5 A L 5 F 0.9085 

 6 A R 6 F 0.8282 

 7 A R 7 M 0.8468 

 8 A R 8 F 0.7430 

 9 A R 9 F 0.7945 

 10 A R 10 F 0.8475 

 11 A R 11 M 0.9188 

 12 A R 12 M 0.8337 

 13 A R 13 F 0.8254 

 4808 14 1 A L 1 M 0.8765 

 2 A L 2 M 0.8406 

 3 A L 3 F 0.7655 

 4 A L 4 M 0.8192 

 5 A L 5 M 0.8560 

 6 A L 6 M 0.9250 

 7 A L 7 F 0.8788 

 8 A L 8 F 0.8942 

 9 A R 9 F 0.8507 

 10 A R 10 F 0.8718 

 11 A R 11 M 0.8882 

 12 A R 12 F 0.9554 

 13 A R 13 M 0.9473 

 14 A R 14 M 0.8788 

 4809 19 1 A L 1 M 0.8810 

 2 A L 2 M 0.8340 

 3 A L 3 F 0.7542 

 4 A L 4 M 0.8357 

 5 A L 5 M 0.8400 

 6 A L 6 F 0.8336 

 7 A L 7 M 0.8674 

 8 A L 8 M 0.8963 

 9 A R 9 F 0.7561 

 10 A R 10 F 0.7887 

 11 A R 11 M 0.7948 

 12 A R 12 F 0.8452 

 13 E R 

 14 A R 13 F 0.8102 

 15 A R 14 F 0.8396 

 16 A R 15 M 0.8383 

 17 A R 16 F 0.7813 

 18 A R 17 F 0.7973 

 19 A R 18 F 0.7978 
Appendix II 28 

Table A-4. Individual Embryo/Fetal Data (page 18 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

20000 4810 13 1 A L 1 F 0.7567 

 2 A L 2 M 0.8425 

 3 A L 3 M 0.8637 

 4 A L 4 M 0.9020 

 5 A L 5 F 0.8044 

 6 A L 6 F 0.8863 

 7 A L 7 M 0.9203 

 8 A R 8 F 0.7931 

 9 A R 9 M 0.8795 

 10 A R 10 F 0.8196 

 11 A R 11 F 0.8692 

 12 A R 12 M 0.8416 

 13 A R 13 F 0.8331 

 4811 13 1 A L 1 F 1.1239 

 2 A L 2 F 1.1188 

 3 A L 3 F 1.1692 

 4 A L 4 M 1.2309 

 5 A L 5 F 1.1065 

 6 D L 0.8750 

 7 A L 6 F 1.1848 

 8 A R 7 F 1.2355 

 9 A R 8 F 1.2401 

 10 A R 9 F 1.1965 

 11 A R 10 F 1.1526 

 12 A R 11 M 1.2364 

 13 A R 12 M 1.2652 

 4812 14 1 A L 1 M 0.9838 

 2 A L 2 F 0.9007 

 3 A L 3 F 0.8484 

 4 A L 4 M 0.9993 

 5 A L 5 F 0.8709 

 6 A R 6 M 0.9528 

 7 A R 7 F 0.8973 

 8 A R 8 F 0.8975 

 9 A R 9 F 0.9014 

 10 A R 10 F 0.8079 

 11 A R 11 F 0.7973 

 12 A R 12 M 1.0232 

 4813 16 1 A L 1 M 1.1349 

 2 A L 2 M 1.0482 

 3 A L 3 M 1.1813 

 4 A L 4 F 1.1449 

 5 E L 

 6 A R 5 M 1.1067 

 7 A R 6 F 1.0247 

 8 A R 7 F 0.9778 

 9 A R 8 F 0.9348 

 10 A R 9 F 0.9969 

 11 A R 10 F 0.9783 

 12 A R 11 F 1.0145 

 13 A R 12 F 1.0523 

 14 A R 13 F 0.9525 

 15 A R 14 F 0.9687 

 16 A R 15 F 0.9585 
Appendix II 29 

Table A-4. Individual Embryo/Fetal Data (page 19 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

20000 4814 9 1 M L 

 2 A L 1 F 1.2799 

 3 A L 2 F 1.3151 

 4 A L 3 M 1.3496 

 5 E L 

 6 A L 4 F 1.1992 

 7 A R 5 M 1.3070 

 8 A R 6 M 1.2653 

 9 E R 

 4815 .g 

 4816 13 1 A L 1 M 0.8639 

 2 A L 2 M 0.9429 

 3 A L 3 F 0.8220 

 4 A L 4 M 0.8379 

 5 A L 5 M 0.9266 

 6 A L 6 F 0.9481 

 7 A L 7 F 0.9420 

 8 A L 8 F 0.9747 

 9 A R 9 F 1.0099 

 10 A R 10 F 0.8801 

 11 A R 11 F 0.9603 

 12 A R 12 F 0.9483 

 13 A R 13 M 0.9909 

 4817 14 1 A L 1 M 1.0301 

 2 E L 

 3 A L 2 M 1.0935 

 4 A L 3 M 1.0339 

 5 A L 4 M 1.0177 

 6 A L 5 M 0.9907 

 7 A L 6 M 0.9161 

 8 A L 7 F 1.0390 

 9 A R 8 M 1.0381 

 10 A R 9 F 1.0077 

 11 A R 10 M 1.0401 

 12 A R 11 F 0.9537 

 13 A R 12 F 0.9633 

 4818 14 1 I L 

 2 I L 

 3 I L 

 4 I L 

 5 I L 

 6 I L 

 7 I R 

 8 I R 

 9 I R 

 10 I R 

 11 I R 

 12 I R 

 13 I R 

 14 I R 

 15 I R 

 16 I R 

 17 I R 
Appendix II 30 

Table A-4. Individual Embryo/Fetal Data (page 20 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

20000 4819 5 1 I L 

 2 I L 

 3 I L 

 4 I R 

 5 I R 

 6 I R 

 7 I R 

 8 I R 

 9 I R 

 10 I R 

 4820 13 1 A L 1 F 0.9712 

 2 A L 2 F 0.9335 

 3 A L 3 F 0.9432 

 4 A L 4 F 0.9313 

 5 A L 5 F 0.7709 

 6 A L 6 M 1.0237 

 7 A L 7 F 0.9602 

 8 A L 8 M 0.9823 

 9 A R 9 M 0.9386 

 10 E R 

 11 A R 10 F 0.9344 

 12 A R 11 F 0.9133 

 4821 15 1 A L 1 M 0.8292 

 2 A L 2 F 0.8331 

 3 A L 3 F 0.7993 

 4 A R 4 M 0.8301 

 5 A R 5 M 0.7856 

 6 A R 6 M 0.6891 

 7 A R 7 F 0.7089 External Malformation Cleft Palate 

 8 A R 8 M 0.5875 

 9 A R 9 M 0.7899 

 10 D R 0.6560 

 11 A R 10 M 0.8427 

 12 A R 11 M 0.8427 

 13 A R 12 M 0.8158 

 14 A R 13 F 0.7604 

 15 A R 14 M 0.7674 

 4822 12 1 A L 1 F 0.9253 

 2 A L 2 M 0.9153 

 3 A L 3 F 0.9479 External Variation Abnormal Rugae in Midline of Palate 

 4 A L 4 M 0.9499 

 5 A R 5 F 0.9415 

 6 A R 6 F 0.8508 

 7 A R 7 M 0.9713 

 8 A R 8 M 0.9437 

 9 A R 9 F 0.8754 

 10 A R 10 M 0.8642 

 11 A R 11 F 0.8712 

 4823 12 1 A L 1 F 0.7820 

 2 A L 2 F 0.8031 

 3 A L 3 M 0.8638 

 4 E L 

 5 A L 4 M 0.9099 

 6 A L 5 M 0.6567 

 7 A R 6 F 0.9373 

 8 A R 7 F 0.8679 

 9 A R 8 F 0.9426 

 10 A R 9 F 0.9749 

 11 A R 10 F 0.8428 

 12 A R 11 M 0.9194 
Appendix II 31 

Table A-4. Individual Embryo/Fetal Data (page 21 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

30000 5801 .g 

 5802 13 1 A L 1 M 0.9804 

 2 A L 2 M 1.1120 

 3 A L 3 M 1.0901 

 4 A R 4 M 1.0564 

 5 A R 5 M 1.0590 

 6 A R 6 F 0.9079 

 7 A R 7 F 0.9483 

 8 A R 8 F 0.9521 

 9 A R 9 F 0.9818 

 10 A R 10 F 0.9639 

 11 A R 11 M 1.0117 

 12 L R 

 13 A R 12 M 0.9321 

 5803 13 1 A L 1 F 1.1267 

 2 A L 2 M 1.1515 

 3 A L 3 M 1.0179 

 4 A L 4 M 1.1013 

 5 A L 5 M 1.0478 

 6 A L 6 M 1.1700 

 7 A R 7 F 1.1515 

 8 A R 8 M 1.2303 

 9 A R 9 F 1.1074 

 10 A R 10 F 1.2296 

 11 M R 

 12 A R 11 M 1.0830 

 13 A R 12 M 1.1170 

 5804 15 1 A L 1 M 1.1464 

 2 A L 2 M 1.0855 

 3 A L 3 M 0.7745 External Malformation Cleft Palate 

 4 A L 4 M 1.0201 

 5 A L 5 F 1.1951 

 6 A R 6 F 0.9255 

 7 A R 7 M 1.2088 

 8 M R 

 9 A R 8 M 1.1263 

 10 A R 9 F 1.0717 

 11 A R 10 M 1.1267 

 12 A R 11 M 1.0228 

 13 A R 12 F 1.1004 

 5805 13 1 A L 1 M 1.0774 

 2 A L 2 F 0.9531 

 3 A L 3 F 0.9565 

 4 A L 4 M 0.9550 

 5 A L 5 F 0.8124 

 6 A L 6 M 1.0683 

 7 A L 7 F 1.0170 

 8 A L 8 M 1.0931 

 9 A R 9 F 1.0089 

 10 A R 10 M 1.0940 

 11 A R 11 F 1.0375 

 12 A R 12 M 1.0142 

 13 A R 13 M 1.0256 
Appendix II 32 

Table A-4. Individual Embryo/Fetal Data (page 22 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

30000 5806 18 1 A L 1 M 0.9533 

 2 A L 2 F 0.9073 

 3 A L 3 M 0.9066 

 4 A L 4 F 0.9136 

 5 A L 5 F 1.0194 

 6 L L 

 7 A L 6 F 0.9655 

 8 A L 7 M 1.0357 

 9 A L 8 F 0.9715 

 10 A L 9 M 0.9788 

 11 A L 10 M 1.0303 

 12 A R 11 F 1.0017 

 13 A R 12 F 0.9086 

 14 A R 13 M 1.0746 

 15 A R 14 M 1.1079 

 16 E R 

 17 A R 15 F 0.9868 

 18 A R 16 F 0.9189 

 5807 13 1 A L 1 F 0.9649 

 2 A L 2 F 0.9225 

 3 A L 3 F 1.0054 

 4 A L 4 F 1.0138 

 5 A L 5 M 1.0280 

 6 A L 6 F 1.0273 

 7 A R 7 F 0.9359 

 8 A R 8 F 0.9338 

 9 A R 9 F 0.9303 

 10 A R 10 M 1.0376 

 11 A R 11 F 0.9072 

 12 A R 12 F 0.8520 

 13 A R 13 M 0.9406 

 5808 13 1 A L 1 M 0.9483 

 2 A L 2 F 1.0104 

 3 A L 3 M 1.0077 

 4 A R 4 M 0.9191 

 5 A R 5 M 0.8189 

 6 A R 6 M 0.9226 

 7 A R 7 M 0.7506 

 8 A R 8 M 0.8968 

 9 A R 9 M 0.9360 

 10 A R 10 F 0.9469 

 11 A R 11 F 0.9655 

 12 A R 12 F 0.9790 

 13 A R 13 M 0.9588 

 5809 16 1 A L 1 M 0.8884 

 2 A L 2 M 0.8127 

 3 A L 3 M 0.8462 

 4 A L 4 M 0.9215 

 5 A L 5 F 0.9343 

 6 E L 

 7 A R 6 F 0.8106 

 8 A R 7 F 0.8068 

 9 A R 8 M 0.8612 

 10 L R 

 11 A R 9 F 0.9078 

 12 A R 10 F 0.8592 

 13 A R 11 M 0.9218 

 14 L R 

 15 A R 12 F 0.8428 

 16 A R 13 M 0.8899 
Appendix II 33 

Table A-4. Individual Embryo/Fetal Data (page 23 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

30000 5810 15 1 A L 1 F 0.8985 

 2 A L 2 F 0.9065 

 3 A L 3 F 0.9001 

 4 A L 4 F 0.9440 

 5 E L 

 6 A L 5 F 0.9382 External Malformation Cleft Palate 

 7 A L 6 F 0.6057 External Malformation Cleft Palate 

 External Malformation Gastroschisis 

 8 A L 7 M 0.8893 

 9 A R 8 F 0.8080 

 10 A R 9 F 0.8684 

 11 A R 10 F 0.8034 

 12 A R 11 M 0.8844 

 13 A R 12 M 0.8406 External Malformation Cleft Palate 

 14 A R 13 F 0.8456 

 15 A R 14 F 0.9768 

 5811 16 1 A L 1 M 0.9681 

 2 A L 2 F 0.9535 

 3 L L 

 4 A L 3 F 1.0411 

 5 A L 4 F 0.9981 

 6 A L 5 F 1.0156 

 7 E L 

 8 A L 6 M 1.1714 

 9 A L 7 M 1.1660 

 10 A R 8 F 1.1421 

 11 A R 9 M 1.1165 

 12 A R 10 M 1.0938 

 13 A R 11 M 1.1929 

 14 A R 12 F 1.1948 

 15 A R 13 M 1.2758 

 16 A R 14 F 1.2000 

 5812 11 1 A L 1 M 1.0452 

 2 A L 2 M 0.9058 

 3 A L 3 F 0.9278 

 4 A L 4 F 1.0021 

 5 A L 5 M 0.9996 

 6 A L 6 M 0.9291 

 7 A L 7 M 1.0208 

 8 A R 8 M 1.0233 

 9 A R 9 M 1.0146 

 10 A R 10 F 0.9597 

 11 A R 11 M 1.0220 

 5813 4 1 I L 

 2 I L 

 3 I L 

 4 I L 

 5 I L 

 6 I R 

 7 I R 

 8 I R 

 9 I R 

 10 I R 

 11 I R 

 12 I R 
Appendix II 34 

Table A-4. Individual Embryo/Fetal Data (page 24 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

30000 5814 12 1 A L 1 M 0.9903 

 2 A L 2 F 0.9792 

 3 A L 3 M 1.0668 

 4 A L 4 F 1.0714 

 5 A L 5 F 1.0852 

 6 A R 6 F 0.8905 

 7 A R 7 M 0.8522 

 8 A R 8 F 0.8659 

 9 A R 9 M 1.0235 

 10 A R 10 F 0.9251 

 11 A R 11 F 1.0418 

 12 A R 12 M 1.0593 

 5815 12 1 A L 1 M 1.1130 

 2 A L 2 F 1.0309 

 3 A L 3 M 1.0280 

 4 A L 4 F 1.0562 

 5 A L 5 F 1.0166 

 6 A L 6 F 1.0871 

 7 A R 7 F 1.0025 

 8 A R 8 M 0.7835 

 9 A R 9 F 1.0818 

 10 A R 10 F 0.9947 

 11 A R 11 F 1.0768 

 12 A R 12 F 0.9457 

 5816 14 1 A L 1 M 1.3655 

 2 A L 2 F 1.2790 

 3 D L 0.8132 

 4 A L 3 F 1.2630 

 5 A L 4 F 1.1545 

 6 A L 5 F 1.2992 

 7 A L 6 M 1.2512 

 8 A R 7 M 1.3040 

 9 A R 8 M 1.2248 

 10 A R 9 F 1.2875 

 11 A R 10 M 1.3026 

 12 E R 

 13 A R 11 F 1.2087 

 14 A R 12 F 1.3550 

 5817 .g 

 5818 16 1 A L 1 F 0.8573 

 2 A L 2 F 0.8314 

 3 A L 3 M 0.8302 

 4 A L 4 F 0.8590 

 5 A L 5 F 0.7868 

 6 A L 6 F 0.9320 

 7 A L 7 F 0.9167 

 8 A L 8 F 0.8636 

 9 A R 9 F 0.8699 

 10 A R 10 F 0.8666 

 11 A R 11 M 0.7944 

 12 A R 12 M 0.8529 

 13 A R 13 F 0.8398 

 14 A R 14 M 0.8448 

 15 A R 15 M 0.8584 
Appendix II 35 

Table A-4. Individual Embryo/Fetal Data (page 25 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

30000 5819 14 1 A L 1 F 1.3938 

 2 A L 2 M 1.4852 

 3 A R 3 F 1.2505 

 4 A R 4 M 1.3148 

 5 A R 5 M 1.1664 

 6 A R 6 F 0.8750 

 7 A R 7 M 1.3726 

 8 E R 

 9 A R 8 M 1.1908 

 10 A R 9 M 1.4493 

 11 A R 10 M 1.3387 

 12 A R 11 M 1.3200 

 5820 13 1 L L 

 2 A L 1 F 0.9656 

 3 A L 2 M 1.0512 

 4 A L 3 F 0.9488 

 5 A L 4 F 0.9156 

 6 A L 5 F 1.0114 

 7 A R 6 F 0.9614 

 8 E R 

 9 A R 7 F 0.9043 

 10 A R 8 F 0.8433 

 11 A R 9 F 0.8728 

 12 A R 10 F 0.9826 

 13 M R 

 14 A R 11 F 0.9827 

 5821 17 1 A L 1 F 1.0300 

 2 A L 2 F 0.9014 

 3 A L 3 M 0.9976 

 4 A L 4 M 1.0325 

 5 E L 

 6 A L 5 F 0.8470 

 7 A L 6 M 1.0474 

 8 E L 

 9 A R 7 M 1.0702 

 10 A R 8 F 1.0475 

 11 A R 9 F 0.9996 

 12 A R 10 M 1.0595 

 13 A R 11 F 0.9625 

 14 A R 12 F 1.0545 

 5822 11 1 A L 1 F 1.0140 

 2 A L 2 F 1.0250 

 3 A R 3 F 0.9620 

 4 A R 4 M 0.9893 

 5 A R 5 F 0.8717 

 6 A R 6 M 0.9655 

 7 A R 7 M 0.9312 

 8 A R 8 F 1.0055 

 9 A R 9 M 1.0297 

 10 A R 10 F 0.9577 

 11 A R 11 F 0.9520 
Appendix II 36 

Table A-4. Individual Embryo/Fetal Data (page 26 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

30000 5823 13 1 A L 1 M 1.5475 

 2 A L 2 F 1.3667 

 3 A L 3 F 1.2577 

 4 A L 4 M 1.4539 

 5 A L 5 M 1.3758 

 6 A L 6 F 1.4071 

 7 A L 7 F 1.3181 

 8 A L 8 F 1.3916 

 9 A R 9 F 1.4486 

 10 A R 10 M 1.3247 

 11 A R 11 F 1.2217 

 12 A R 12 M 1.4355 

 13 A R 13 M 1.4881 

 5824 5 1 I R 

 2 I R 

 3 I R 

 4 I R 

 5825 11 1 A L 1 M 1.0203 

 2 A L 2 F 0.9395 

 3 A L 3 F 0.9975 

 4 A L 4 F 0.9981 

 5 A L 5 F 1.0025 

 6 A L 6 M 0.8743 

 7 A L 7 F 0.9600 

 8 A R 8 F 1.1533 

 9 E R 

 10 A R 9 M 1.0698 

 11 A R 10 M 1.0630 

 5826 16 1 A L 1 M 0.8428 

 2 A L 2 M 0.9350 

 3 A L 3 F 0.9731 

 4 A L 4 M 1.0226 

 5 A L 5 M 0.9213 

 6 A L 6 M 0.8604 

 7 A R 7 F 0.8411 

 8 A R 8 F 0.9784 

 9 A R 9 M 0.8939 

 10 A R 10 F 0.8954 

 11 A R 11 F 0.8163 

 12 A R 12 M 0.9026 

 13 A R 13 M 0.8072 

 14 A R 14 F 0.8687 

 5827 14 1 A L 1 M 0.9385 

 2 A L 2 F 0.9648 

 3 A L 3 M 0.9358 

 4 A L 4 F 0.7844 

 5 A R 5 F 0.9408 

 6 A R 6 F 0.9805 

 7 A R 7 F 1.0502 

 8 A R 8 F 0.8167 

 9 A R 9 M 1.0225 

 10 A R 10 F 0.9819 

 11 A R 11 F 0.9894 
Appendix II 37 

Table A-4. Individual Embryo/Fetal Data (page 27 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

30000 5828 11 1 A L 1 F 0.9467 

 2 A L 2 F 0.9957 

 3 A L 3 F 0.8725 

 4 A L 4 F 0.8279 

 5 A L 5 F 0.9775 

 6 A L 6 F 1.0164 External Malformation Cleft Palate 

 7 A L 7 M 0.8595 

 8 A L 8 F 0.9852 

 9 A R 9 F 0.8664 

 10 A R 10 F 0.9977 

 11 E R 

 12 A R 11 F 0.9024 

 5829 14 1 A L 1 F 1.1204 

 2 E L 

 3 A L 2 F 1.1703 

 4 A L 3 F 1.1694 

 5 A R 4 M 1.1893 

 6 A R 5 M 1.1602 

 7 A R 6 M 1.1989 

 8 A R 7 M 1.1962 

 9 A R 8 F 1.1228 

 10 E R 

 11 A R 9 M 1.1192 

 5830 15 1 A L 1 M 1.0950 

 2 A L 2 F 1.1618 

 3 A L 3 M 1.0445 

 4 A L 4 F 1.0395 

 5 A R 5 F 1.2304 

 6 A R 6 F 1.0734 

 7 A R 7 M 0.9946 External Malformation Cleft Palate 

 8 A R 8 M 1.1270 

 9 A R 9 M 0.9994 

 10 A R 10 F 1.1301 

 11 A R 11 F 1.0525 External Malformation Cleft Palate 

 12 A R 12 M 0.9878 

 13 A R 13 F 1.0706 

 5831 14 1 A L 1 F 0.9588 

 2 A L 2 M 1.0149 

 3 A L 3 M 0.9975 

 4 A L 4 F 0.8350 

 5 A L 5 F 0.9145 

 6 A L 6 M 1.0151 

 7 A R 7 M 0.9522 

 8 A R 8 F 0.9081 

 9 A R 9 F 0.8420 

 10 A R 10 M 0.9452 

 11 A R 11 F 0.8850 

 12 A R 12 M 0.9097 

 13 A R 13 M 0.9792 
Appendix II 38 

Table A-4. Individual Embryo/Fetal Data (page 28 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

30000 5832 14 1 A L 1 M 1.1667 

 2 A L 2 F 1.0426 

 3 A L 3 F 1.0582 

 4 A L 4 F 0.9516 

 5 A L 5 F 0.9912 

 6 A L 6 F 0.9265 

 7 A L 7 M 1.0659 

 8 A L 8 M 1.1146 

 9 A L 9 F 1.0422 

 10 A R 10 F 1.0611 

 11 A R 11 M 1.1725 

 12 A R 12 M 1.1148 

 13 A R 13 F 1.1144 

 14 A R 14 M 1.0441 

 5833 16 1 A L 1 M 0.9488 

 2 A L 2 F 0.8791 

 3 E L 

 4 A L 3 F 0.8688 

 5 A L 4 F 0.7998 

 6 E L 

 7 A L 5 M 0.8976 

 8 A L 6 F 0.9030 

 9 A R 7 F 0.8906 

 10 A R 8 F 0.8321 

 11 A R 9 F 0.8715 

 12 A R 10 F 0.8348 

 13 A R 11 M 0.8665 

 14 A R 12 F 0.9051 

 5834 10 1 A L 1 M 0.9527 

 2 A L 2 F 0.9792 

 3 A L 3 M 0.9705 

 4 A L 4 M 0.8064 

 5 A L 5 M 1.0083 

 6 A L 6 M 0.9922 

 7 A L 7 F 0.9961 

 8 A R 8 M 1.0352 

 9 A R 9 M 0.9722 

 10 A R 10 F 1.0271 

 5835 12 1 A L 1 F 1.5416 

 2 E L 

 3 A L 2 M 1.5103 

 4 A L 3 M 1.4931 

 5 A L 4 M 1.1562 

 6 A R 5 M 1.2581 

 7 A R 6 F 1.4263 

 8 A R 7 F 1.5269 

 9 A R 8 F 1.4091 

 10 A R 9 M 1.5567 

 11 A R 10 F 1.3408 

 12 A R 11 F 1.3742 

 13 A R 12 M 1.5313 
Appendix II 39 

Table A-4. Individual Embryo/Fetal Data (page 29 of 29) 

 Implant 

 Dam Posi- Fetus Defectf

Dosea ID# NCLb # Typec tiond # Sex Wt.e Exam Type Description 

30000 5836 13 1 A L 1 F 0.9538 

 2 A L 2 M 0.9240 

 3 A L 3 F 0.8944 

 4 A L 4 M 0.9606 

 5 A L 5 F 0.9417 

 6 A L 6 M 0.8582 

 7 A L 7 M 0.9532 

 8 A R 8 F 0.8749 

 9 A R 9 F 1.0230 

 10 A R 10 F 0.9640 

 11 A R 11 M 0.8196 

 12 A R 12 M 0.9105 

 13 A R 13 F 0.8231 

 14 A R 14 M 1.0398 

 5837 15 1 I L 

 2 I L 

 3 I L 

 4 I L 

 5 I L 

 6 I R 

 7 I R 

 8 I R 

 9 I R 

 10 I R 

 11 I R 

 12 I R 

 13 I R 

 5838 13 1 A L 1 M 1.0087 

 2 A L 2 F 0.9374 

 3 A L 3 M 0.8882 

 4 A L 4 M 0.9084 

 5 A L 5 F 0.8730 

 6 L L 

 7 A L 6 M 0.9249 

 8 A L 7 M 0.9987 

 9 A L 8 F 0.9615 

 10 A L 9 F 0.9365 

 11 A R 10 M 1.0784 

 12 A R 11 F 1.0335 

 13 A R 12 F 1.0152 

 14 E R 

aMg/m3 of gasoline MTBE vapor condensate. bNumber of corpora lutea. 

cImplant type codes are as follows: A - Live Fetus; D - Dead Fetus; F - Full Resorption; L - Late Resorption; M - 

Middle Resorption; E - Early Resorption and I - Implantation Site. 

dPosition refers to uterine horn (R - right, L - left). 

eWeight is in grams. 

f

Absence of entries under "Exam", "Type" and "Description" for "Defect" indicates no external malformation or 

variation observed for that fetus. 

gFemale was not pregnant. 

hFemale was removed due to a preexisting condition. At necropsy she was found to have an undescended testis on 

the right and seminal vesicles and prostate to the right of the vagina and cervix. i

Right ovary was inadvertently lost prior to the corpora lutea being counted. 
Appendix III: 

Protocol and 2 Amendments